{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:48:17Z","timestamp":1791575297045,"version":"4.3.4"},"reference-count":157,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Brain organoids are three-dimensional cultures that contain multiple types of cells and cytoarchitectures, and resemble fetal human brain structurally and functionally. These organoids are being used increasingly to model brain development and disorders, however, they only partially recapitulate such processes, because of several limitations, including inability to mimic the distinct cortical layers, lack of functional neuronal circuitry as well as non-neural cells and gyrification, and increased cellular stress. Efforts to create improved brain organoid culture systems have led to region-specific organoids, vascularized organoids, glia-containing organoids, assembloids, sliced organoids and polarized organoids. Assembloids are fused region-specific organoids, which attempt to recapitulate inter-regional and inter-cellular interactions as well as neural circuitry development by combining multiple brain regions and\/or cell lineages. As a result, assembloids can be used to model subtle functional aberrations that reflect complex neurodevelopmental, neuropsychiatric and neurodegenerative disorders. Mammalian organisms possess a highly complex neuroendocrine system, the stress system, whose main task is the preservation of systemic homeostasis, when the latter is threatened by adverse forces, the stressors. The main central parts of the stress system are the paraventricular nucleus of the hypothalamus and the locus caeruleus\/norepinephrine-autonomic nervous system nuclei in the brainstem; these centers innervate each other and interact reciprocally as well as with various other CNS structures. Chronic dysregulation of the stress system has been implicated in major pathologies, the so-called chronic non-communicable diseases, including neuropsychiatric, neurodegenerative, cardiometabolic and autoimmune disorders, which lead to significant population morbidity and mortality. We speculate that brain organoids and\/or assembloids could be used to model the development, regulation and dysregulation of the stress system and to better understand stress-related disorders. Novel brain organoid technologies, combined with high-throughput single-cell omics and gene editing, could, thus, have major implications for precision medicine.<\/jats:p>","DOI":"10.3389\/fphys.2021.621970","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T09:18:24Z","timestamp":1623316704000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":46,"title":["From Brain Organoids to Networking Assembloids: Implications for Neuroendocrinology and Stress Medicine"],"prefix":"10.3389","volume":"12","author":[{"given":"Evanthia A.","family":"Makrygianni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George P.","family":"Chrousos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.neuron.2017.03.042","article-title":"iPSC-derived human microglia-like cells to study neurological diseases.","volume":"94","author":"Abud","year":"2017","journal-title":"Neuron"},{"key":"B2","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1152\/physiol.00005.2019","article-title":"Brain organoids as tools for modeling human neurodevelopmental disorders.","volume":"34","author":"Adams","year":"2019","journal-title":"Physiology (Bethesda, Md.)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/nature12064","article-title":"The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line.","volume":"500","author":"Adey","year":"2013","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/jne.12547","article-title":"Understanding the role of steroids in typical and atypical brain development: advantages of using a \u201cbrain in a dish\u201d sapproach.","volume":"30","author":"Adhya","year":"2018","journal-title":"J. Neuroendocrinol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"3978","DOI":"10.1002\/1873-3468.12924","article-title":"Cerebral cortex development: an outside-in perspective.","volume":"591","author":"Agirman","year":"2017","journal-title":"FEBS Lett."},{"key":"B6","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/nature08792","article-title":"Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients.","volume":"464","author":"Agarwal","year":"2010","journal-title":"Nature"},{"key":"B7","author":"Alberts","year":"2002","journal-title":"Molecular Biology of the Cell. Blood Vessels and Endothelial Cells"},{"key":"B8","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.neuron.2018.10.007","article-title":"Building models of brain disorders with three-dimensional organoids.","volume":"100","author":"Amin","year":"2018","journal-title":"Neuron"},{"key":"B9","doi-asserted-by":"publisher","first-page":"3825","DOI":"10.1093\/hmg\/dds211","article-title":"Evidence for premature aging due to oxidative stress in iPSCs from Cockayne syndrome.","volume":"21","author":"Andrade","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.semcdb.2020.05.022","article-title":"Taming human brain organoids one cell at a time.","volume":"111","author":"Atamian","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1124\/pr.111.005108","article-title":"Brain-derived neurotrophic factor and neuropsychiatric disorders.","volume":"64","author":"Autry","year":"2012","journal-title":"Pharmacol. Rev."},{"key":"B12","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1038\/nmeth.4304","article-title":"Fused cerebral organoids model interactions between brain regions.","volume":"14","author":"Bagley","year":"2017","journal-title":"Nat.Methods"},{"key":"B13","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/nature10084","article-title":"Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells.","volume":"474","author":"Batista","year":"2011","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/s41586-020-1962-0","article-title":"Cell stress in cortical organoids impairs molecular subtype specification.","volume":"578","author":"Bhaduri","year":"2020","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1007\/s10286-005-0290-7","article-title":"Paraventricular nucleus, stress response, and cardiovascular disease.","volume":"15","author":"Benarroch","year":"2005","journal-title":"Clin. Autonomic Res. Official J. Clin. Auto. Res. Soc."},{"key":"B16","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1212\/WNL.0b013e31823fcdee","article-title":"Periaqueductal gray: an interface for behavioral control.","volume":"78","author":"Benarroch","year":"2012","journal-title":"Neurology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1002\/wdev.187","article-title":"Patterning, specification, and differentiation in the developing hypothalamus.","volume":"4","author":"Bedont","year":"2015","journal-title":"Wiley Interdisciplinary Rev. Dev. Biol."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a035709","article-title":"Brain Organoids: Human Neurodevelopment in a Dish.","volume":"12","author":"Benito-Kwiecinski","year":"2019","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1038\/s41596-018-0066-x","article-title":"Blood-brain-barrier organoids for investigating the permeability of CNS therapeutics.","volume":"13","author":"Bergmann","year":"2018","journal-title":"Nat. Protoc."},{"key":"B20","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.stem.2016.12.007","article-title":"Human iPSC-derived cerebral organoids model cellular features of lissencephaly and reveal prolonged mitosis of outer radial glia.","volume":"20","author":"Bershteyn","year":"2017","journal-title":"Cell Stem Cell"},{"key":"B21","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/nature22330","article-title":"Assembly offunctionally integrated human forebrain spheroids.","volume":"545","author":"Birey","year":"2017","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1007\/978-981-13-2835-0_7","article-title":"Extracellular Matrix and Ageing.","volume":"90","author":"Birch","year":"2018","journal-title":"Sub Cell. Biochem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1038\/s41591-018-0139-y","article-title":"Genetically engineered human cortical spheroid models of tuberous sclerosis.","volume":"24","author":"Blair","year":"2018","journal-title":"Nat. Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.ydbio.2007.08.046","article-title":"TCF4 deficiency expands ventral diencephalon signaling and increases induction of pituitary progenitors.","volume":"311","author":"Brinkmeier","year":"2007","journal-title":"Dev. Biol."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0129-z","article-title":"Spatial transcriptomics coming of age.","volume":"2","author":"Burgess","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1038\/s41592-019-0586-5","article-title":"Engineering of human brain organoids with a functional vascular-like system.","volume":"16","author":"Cakir","year":"2019","journal-title":"Nat. Methods"},{"key":"B27","doi-asserted-by":"publisher","first-page":"15672","DOI":"10.1073\/pnas.1520760112","article-title":"Human cerebral organoids recapitulate gene expression programs of fetal neocortex development.","volume":"112","author":"Camp","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1242\/dev.150458","article-title":"Human organomics: a fresh approach to understanding human development using single-cell transcriptomics.","volume":"144","author":"Camp","year":"2017","journal-title":"Development (Cambridge, England)"},{"key":"B29","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/s41587-019-0085-3","article-title":"Specification of positional identity in forebrain organoids.","volume":"37","author":"Cederquist","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"7789","DOI":"10.1007\/s12035-016-0274-8","article-title":"Modeling of Autism using organoid technology.","volume":"54","author":"Choi","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.brainres.2015.11.013","article-title":"Back and forth in time: directing age in iPSC-derived lineages.","volume":"1656","author":"Cornacchia","year":"2017","journal-title":"Brain Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1001\/jama.1992.03480090092034","article-title":"The concepts of stress and stress system disorders.","volume":"267","author":"Chrousos","year":"1992","journal-title":"Overv. Phys. Behav. Homeostasis. JAMA"},{"key":"B33","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/nrendo.2009.106","article-title":"Stress and disorders of the stress system.","volume":"5","author":"Chrousos","year":"2009","journal-title":"Nat. Rev. Endocrinol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.jsmc.2007.04.004","article-title":"Organization and integration of the endocrine system.","volume":"2","author":"Chrousos","year":"2007","journal-title":"Sleep Med. Clin."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1016\/j.cell.2016.05.082","article-title":"Modeling development and disease with organoids.","volume":"165","author":"Clevers","year":"2016","journal-title":"Cell"},{"key":"B36","doi-asserted-by":"publisher","first-page":"141","DOI":"10.2174\/1570159X11311020002","article-title":"Mechanisms in the bed nucleus of the stria terminalis involved in control of autonomic and neuroendocrine functions: a review.","volume":"11","author":"Crestani","year":"2013","journal-title":"Curr. Neuropharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/nature18296","article-title":"The Brazilian Zika virus strain causes birth defects in experimental models.","volume":"534","author":"Cugola","year":"2016","journal-title":"Nature"},{"key":"B38","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.stem.2016.04.014","article-title":"Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3.","volume":"19","author":"Dang","year":"2016","journal-title":"Cell Stem Cell"},{"key":"B39","doi-asserted-by":"publisher","first-page":"ENEURO.0219","DOI":"10.1523\/ENEURO.0219-18.2018","article-title":"Vascularization and engraftment of transplanted human cerebral organoids in mouse cortex.","volume":"5","author":"Daviaud","year":"2018","journal-title":"eNeuro"},{"key":"B40","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1017\/s1092852900013754","article-title":"The subgenual anterior cingulate cortex in mood disorders.","volume":"13","author":"Drevets","year":"2008","journal-title":"CNS Spectrums"},{"key":"B41","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/s41592-019-0692-4","article-title":"Computational methods for single-cell omics across modalities.","volume":"17","author":"Efremova","year":"2020","journal-title":"Nat. Methods"},{"key":"B42","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.stem.2008.09.002","article-title":"Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals.","volume":"3","author":"Eiraku","year":"2008","journal-title":"Cell Stem Cell"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00538","article-title":"Brainstem organoids from human pluripotent stem cells.","volume":"14","author":"Eura","year":"2020","journal-title":"Front. Neurosci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"80","DOI":"10.2174\/157015913804999522","article-title":"The effects of locus coeruleus and norepinephrine in methamphetamine toxicity.","volume":"11","author":"Ferrucci","year":"2013","journal-title":"Curr. Neuropharmacol."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00558","article-title":"Genetic modification of brain organoids.","volume":"13","author":"Fischer","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3791\/55372","article-title":"Generation of iPSC-derived human brain organoids to model early neurodevelopmental disorders.","volume":"14","author":"Gabriel","year":"2017","journal-title":"J. Visualized Exp. JoVE"},{"key":"B47","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1126\/science.aaf6116","article-title":"Zika virus impairs growth in human neurospheres and brain organoids.","volume":"352","author":"Garcez","year":"2016","journal-title":"Science (New York, N.Y.)"},{"key":"B48","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/sj.mp.4001032","article-title":"Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH\/NE states.","volume":"7","author":"Gold","year":"2002","journal-title":"Mol. Psychiatry"},{"key":"B49","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/mp.2014.163","article-title":"The organization of the stress system and its dysregulation in depressive illness.","volume":"20","author":"Gold","year":"","journal-title":"Mol. Psychiatry"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/581976","article-title":"Clinical and biochemical manifestations of depression: relation to the neurobiology of stress.","volume":"2015","author":"Gold","year":"","journal-title":"Neural Plasticity"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2019.00320","article-title":"A major role for the lateral habenula in depressive illness: physiologic and molecular mechanisms.","volume":"10","author":"Gold","year":"2019","journal-title":"Front. Psychiatry"},{"key":"B52","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1038\/s41380-018-0229-8","article-title":"Modeling amyloid beta and tau pathology in human cerebral organoids.","volume":"23","author":"Gonzalez","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"B53","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1101\/lm.044206.116","article-title":"Role of the bed nucleus of the stria terminalis in aversive learning and memory.","volume":"24","author":"Goode","year":"2017","journal-title":"Learn. Memory (Cold Spring Harbor, N.Y.)"},{"key":"B54","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/s41380-019-0500-7","article-title":"Three-dimensional modeling of human neurodegeneration: brain organoids coming of age.","volume":"25","author":"Grenier","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"B55","article-title":"Neuroanatomy of reward: a view from the ventral striatum","author":"Haber","year":"2011","journal-title":"Neurobiology of Sensation and Reward"},{"key":"B56","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1007\/s10571-012-9827-1","article-title":"Stress-related serotonergic systems: implications for symptomatology of anxiety and affective disorders.","volume":"32","author":"Hale","year":"2012","journal-title":"Cell. Mol. Neurobiol."},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2014.00015","article-title":"Evolution of the human brain: when bigger is better.","volume":"8","author":"Hofman","year":"2014","journal-title":"Front. Neuroanatomy"},{"key":"B58","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.jchemneu.2003.10.002","article-title":"The human raphe nuclei and the serotonergic system.","volume":"26","author":"Hornung","year":"2003","journal-title":"J. Chem. Neuroanat."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2014.00073","article-title":"Contributions of the paraventricular thalamic nucleus in the regulation of stress, motivation, and mood.","volume":"8","author":"Hsu","year":"2014","journal-title":"Front. Behav. Neurosci."},{"key":"B60","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1083\/jcb.201709054","article-title":"Opportunities for organoids as new models of aging.","volume":"217","author":"Hu","year":"2018","journal-title":"J. Cell Biol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.celrep.2017.03.047","article-title":"An organoid-based model of cortical development identifies non-cell-autonomous defects in wnt signaling contributing to miller-dieker syndrome.","volume":"19","author":"Iefremova","year":"2017","journal-title":"Cell Rep."},{"key":"B62","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.stem.2016.07.005","article-title":"Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin-producing neurons.","volume":"19","author":"Jo","year":"2016","journal-title":"Cell Stem Cell"},{"key":"B63","doi-asserted-by":"publisher","first-page":"20284","DOI":"10.1073\/pnas.1315710110","article-title":"Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex.","volume":"110","author":"Kadoshima","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B64","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1038\/s41567-018-0046-7","article-title":"Human brain organoids on a chip reveal the physics of folding.","volume":"14","author":"Karzbrun","year":"2018","journal-title":"Nat. Phys."},{"key":"B65","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.celrep.2019.12.009","article-title":"Hypothalamic contribution to pituitary functions is recapitulated In Vitro Using 3D-cultured human iPS cells.","volume":"30","author":"Kasai","year":"2020","journal-title":"Cell Rep."},{"key":"B66","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1001\/jamapsychiatry.2020.0196","article-title":"Transcriptomic landscape and functional characterization of induced pluripotent stem cell-derived cerebral organoids in schizophrenia.","volume":"77","author":"Kathuria","year":"2020","journal-title":"JAMA Psychiatry"},{"key":"B67","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1210\/er.2009-0008","article-title":"Genetic regulation of pituitary gland development in human and mouse.","volume":"30","author":"Kelberman","year":"2009","journal-title":"Endocrine Rev."},{"key":"B68","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.stemcr.2019.01.020","article-title":"Modeling G2019S-LRRK2 sporadic parkinson\u2019s disease in 3D midbrain organoids.","volume":"12","author":"Kim","year":"2019","journal-title":"Stem Cell Rep."},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31256-1","article-title":"Efficient derivation of sympathetic neurons from human pluripotent stem cells with a defined condition.","volume":"8","author":"Kirino","year":"2018","journal-title":"Sci. Rep."},{"key":"B70","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1002\/stem.3163","article-title":"Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson\u2019s disease modeling.","volume":"38","author":"Kwak","year":"2020","journal-title":"Stem Cells (Dayton, Ohio)"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.039347","article-title":"Disease modelling in human organoids.","volume":"12","author":"Lancaster","year":"2019","journal-title":"Dis. Models Mech."},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247125","article-title":"Organogenesis in a dish: modeling development and disease using organoid technologies.","volume":"345","author":"Lancaster","year":"2014","journal-title":"Science"},{"key":"B73","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nature12517","article-title":"Cerebral organoids model human brain development and microcephaly.","volume":"501","author":"Lancaster","year":"2013","journal-title":"Nature"},{"key":"B74","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/mp.2016.1","article-title":"Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders.","volume":"21","author":"Lebow","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163072","article-title":"Three dimensional human neuro-spheroidmodel of Alzheimer\u2019s disease based on differentiated inducedpluripotent stem cells.","volume":"11","author":"Lee","year":"2016","journal-title":"PLoS ONE"},{"key":"B76","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.1111\/febs.15282","article-title":"The ECM path of senescence in aging: components and modifiers.","volume":"287","author":"Levi","year":"2020","journal-title":"FEBS J."},{"key":"B77","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.stem.2016.11.017","article-title":"Induction of expansion and folding in human cerebral organoids.","volume":"20","author":"Li","year":"","journal-title":"Cell Stem Cell"},{"key":"B78","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1007\/s13238-017-0479-2","article-title":"Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindlelike (ASPM related primary) microcephaly disease.","volume":"8","author":"Li","year":"","journal-title":"Protein Cell"},{"key":"B79","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/nri.2017.125","article-title":"Microglia and macrophages in brain homeostasis and disease.","volume":"18","author":"Li","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.06.011","article-title":"APOE4 causes widespread molecular and cellular alterations associated with Alzheimer\u2019s disease phenotypes in humaniPSCderived brain cell types.","volume":"98","author":"Lin","year":"2018","journal-title":"Neuron."},{"key":"B81","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1002\/cphy.c180025","article-title":"Studying human neurological disorders using induced pluripotent stem cells: from 2D Monolayer to 3D Organoid and Blood Brain Barrier Models.","volume":"9","author":"Logan","year":"2019","journal-title":"Comp. Physiol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"3369","DOI":"10.1016\/j.celrep.2016.12.001","article-title":"Cerebral organoids recapitulate epigenomic signatures of the human fetal brain.","volume":"17","author":"Luo","year":"2016","journal-title":"Cell Rep."},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2016950118","article-title":"Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate.","volume":"118","author":"Lu","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B84","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1038\/s41592-018-0081-4","article-title":"Induction of myelinating oligodendrocytes in human cortical spheroids.","volume":"15","author":"Madhavan","year":"2018","journal-title":"Nat. Methods"},{"key":"B85","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.neubiorev.2020.07.038","article-title":"The role of norepinephrine in the pathophysiology of schizophrenia.","volume":"118","author":"M\u00e4ki-Marttunen","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B86","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1038\/nbt.4127","article-title":"An in vivo model of functional and vascularized human brain organoids.","volume":"36","author":"Mansour","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.cell.2015.06.034","article-title":"FOXG1-dependent dysregulation of GABA\/Glutamate neuron differentiation in autism spectrum disorders.","volume":"162","author":"Mariani","year":"2015","journal-title":"Cell"},{"key":"B88","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.tcb.2019.11.004","article-title":"Organoid and assembloid technologies for investigating cellular crosstalk in human brain development and disease.","volume":"30","author":"Marton","year":"2019","journal-title":"Trends Cell Biol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1038\/s41593-018-0316-9","article-title":"Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures.","volume":"22","author":"Marton","year":"2019","journal-title":"Nat. Neurosci."},{"key":"B90","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1152\/physrev.00041.2006","article-title":"Physiology and neurobiology of stress and adaptation: central role of the brain.","volume":"87","author":"McEwen","year":"2007","journal-title":"Physiol. Rev."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1038\/mp.2017.86","article-title":"MeCP2-regulated miRNAs control early human neurogenesis through differential effects on ERK and AKT signaling.","volume":"23","author":"Mellios","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"B92","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/j.stem.2015.09.001","article-title":"Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects.","volume":"17","author":"Mertens","year":"2015","journal-title":"Cell Stem Cell"},{"key":"B93","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1146\/annurev-genet-120417-031534","article-title":"Aging in a Dish: iPSC-derived and directly induced neurons for studying brain aging and age-related neurodegenerative diseases.","volume":"52","author":"Mertens","year":"2018","journal-title":"Annu. Rev. Genet."},{"key":"B94","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1053\/meta.2002.33184","article-title":"Neuroendocrine aspects of the response to stress.","volume":"51","author":"Miller","year":"2002","journal-title":"Metab. Clin. Exp."},{"key":"B95","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/s41587-019-0084-4","article-title":"Polarizing brain organoids.","volume":"37","author":"Miura","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb2153","article-title":"Transient cortical circuits match spontaneous and sensory-driven activity during development.","volume":"370","author":"Moln\u00e1r","year":"2020","journal-title":"Science (New York, N.Y.)"},{"key":"B97","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1002\/stem.1585","article-title":"Transcription factor-induced lineage programming of noradrenaline and motor neurons from embryonic stem cells.","volume":"32","author":"Mong","year":"2014","journal-title":"Stem Cells (Dayton, Ohio)"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1016\/j.stemcr.2017.03.010","article-title":"Derivation of human midbrain-specific organoids from neuroepithelial stem cells.","volume":"8","author":"Monzel","year":"2017","journal-title":"Stem Cell Rep."},{"key":"B99","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.celrep.2014.12.051","article-title":"Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells.","volume":"10","author":"Muguruma","year":"2015","journal-title":"Cell Rep."},{"key":"B100","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/0301-0082(90)90018-c","article-title":"Development and plasticity of the locus coeruleus: a review of recent physiological and pharmacological experimentation.","volume":"34","author":"Nakamura","year":"1990","journal-title":"Prog. Neurobiol."},{"key":"B101","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/0361-9230(91)90172-g","article-title":"Electrophysiological evidence for axonal degeneration of locus coeruleus neurons following long-term forced running stress.","volume":"26","author":"Nakamura","year":"1991","journal-title":"Brain Res. Bull."},{"key":"B102","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/490171a","article-title":"Epigenetics: stress makes its molecular mark.","volume":"490","author":"Nestler","year":"2012","journal-title":"Nature"},{"key":"B103","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1001\/jamapsychiatry.2013.4291","article-title":"Epigenetic mechanisms of depression.","volume":"71","author":"Nestler","year":"2014","journal-title":"JAMA Psychiatry"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25603-5","article-title":"Human cortex spheroid with a functional blood brain barrier for high-throughput neurotoxicity screening and disease modeling.","volume":"8","author":"Nzou","year":"2018","journal-title":"Sci. Rep."},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22053-x","article-title":"Vasopressin-secreting neurons derived from human embryonic stem cells through specific induction of dorsal hypothalamic progenitors.","volume":"8","author":"Ogawa","year":"2018","journal-title":"Sci. Rep."},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1063\/1.5045124","article-title":"Review: synthetic scaffolds to control the biochemical, mechanical, and geometrical environment of stem cell-derived brain organoids.","volume":"2","author":"Oksdath","year":"2018","journal-title":"APL Bioeng."},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10351","article-title":"Functional anterior pituitary generated in selforganizing culture of human embryonic stem cells.","volume":"7","author":"Ozone","year":"2016","journal-title":"Nat. Commun."},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06684-2","article-title":"Microglia innately develop within cerebral organoids.","volume":"9","author":"Ormel","year":"2018","journal-title":"Nat. Commun."},{"key":"B109","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.tig.2018.06.001","article-title":"Single-Cell Multi-omics: an engine for new quantitative models of gene regulation.","volume":"34","author":"Packer","year":"2018","journal-title":"Trends Genet. TIG"},{"key":"B110","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.3415","article-title":"Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture.","volume":"12","author":"Pasca","year":"2015","journal-title":"Nat. Methods"},{"key":"B111","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1126\/science.aau5729","article-title":"Assembling human brain organoids.","volume":"363","author":"Pa\u015fca","year":"2019","journal-title":"Science"},{"key":"B112","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.neuron.2014.07.002","article-title":"A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei.","volume":"83","author":"Pollak Dorocic","year":"2014","journal-title":"Neuron"},{"key":"B113","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1097\/WNR.0000000000001014","article-title":"Generation of human vascularized brain organoids.","volume":"29","author":"Pham","year":"2018","journal-title":"Neuroreport"},{"key":"B114","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1096\/fj.201801028RR","article-title":"Human fetal adrenal cells retain age-related stem- and endocrine-differentiation potential in culture.","volume":"33","author":"Poli","year":"2019","journal-title":"FASEB J. Official Publication Federation Am. Soc. Exp. Biol."},{"key":"B115","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.tics.2011.12.011","article-title":"Neural circuits underlying the pathophysiology of mood disorders.","volume":"16","author":"Price","year":"2012","journal-title":"Trends Cogn. Sci."},{"key":"B116","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1016\/j.cell.2016.04.032","article-title":"Brain-region-specific organoids using mini-bioreactors for modeling zikv exposure.","volume":"165","author":"Qian","year":"2016","journal-title":"Cell"},{"key":"B117","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/nprot.2017.152","article-title":"Generation of human brain region-specific organoids using a miniaturized spinning bioreactor.","volume":"13","author":"Qian","year":"2018","journal-title":"Nat. Protoc."},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1242\/dev.166074","article-title":"Brain organoids: advances, applications and challenges.","volume":"146","author":"Qian","year":"2019","journal-title":"Development (Cambridge, England)"},{"key":"B119","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/j.stem.2020.02.002","article-title":"Sliced human cortical organoids for modeling distinct cortical layer formation.","volume":"26","author":"Qian","year":"2020","journal-title":"Cell Stem Cell"},{"key":"B120","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/nature22047","article-title":"Cell diversity and network dynamics in photosensitive human brain organoids.","volume":"545","author":"Quadrato","year":"2017","journal-title":"Nature"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161969","article-title":"Self-organizing 3D human neural tissue derived from induced pluripotent stem cells recapitulate Alzheimer\u2019s diseasephenotypes.","volume":"11","author":"Raja","year":"2016","journal-title":"PLoS One"},{"key":"B122","doi-asserted-by":"crossref","first-page":"698.e","DOI":"10.1016\/j.stem.2018.03.009","article-title":"Superobese patient-derived iPSC hypothalamic neurons exhibit obesogenic signatures and hormone responses.","volume":"22","author":"Rajamani","year":"2018","journal-title":"Cell Stem Cell"},{"key":"B123","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1007\/s11154-005-3047-7","article-title":"Early development of the pituitary gland: induction and shaping of Rathke\u2019s pouch.","volume":"6","author":"Rizzoti","year":"2005","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"B124","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/978-3-319-41603-8_11","article-title":"Perspective on Stem Cells in Developmental Biology, with Special Reference to Neuroendocrine Systems","author":"Rizzoti","year":"2016","journal-title":"Stem Cells in Neuroendocrinology"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9896","article-title":"Generation of functional hippocampal neurons from self-organizing human embryonic stem cell-derived dorsomedial telencephalic tissue.","volume":"6","author":"Sakaguchi","year":"2015","journal-title":"Nat. Commun."},{"key":"B126","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1159\/000368279","article-title":"The nucleus accumbens: a comprehensive review.","volume":"93","author":"Salgado","year":"2015","journal-title":"Stereotact. Funct. Neurosurg."},{"key":"B127","doi-asserted-by":"publisher","first-page":"235","DOI":"10.2174\/157015908785777229","article-title":"Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part I: principles of functional organisation.","volume":"6","author":"Samuels","year":"","journal-title":"Curr. Neuropharmacol."},{"key":"B128","doi-asserted-by":"publisher","first-page":"254","DOI":"10.2174\/157015908785777193","article-title":"Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part II: physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans.","volume":"6","author":"Samuels","year":"","journal-title":"Curr. Neuropharmacol."},{"key":"B129","doi-asserted-by":"publisher","first-page":"R1051","DOI":"10.1016\/j.cub.2015.09.039","article-title":"Organization of the locus coeruleus-norepinephrine system.","volume":"25","author":"Schwarz","year":"2015","journal-title":"Curr. Biol. CB"},{"key":"B130","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1126\/science.1062736","article-title":"Pituitary development: regulatory codes in mammalian organogenesis.","volume":"295","author":"Scully","year":"2002","journal-title":"Science"},{"key":"B131","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.ceb.2019.07.010","article-title":"Toward the formation of neural circuits in human brain organoids.","volume":"61","author":"Seto","year":"2019","journal-title":"Curr. Opin. Cell Biol."},{"key":"B132","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/s41592-019-0693-3","article-title":"Single-cell biology: beyond the sum of its parts.","volume":"17","author":"Schier","year":"2020","journal-title":"Nat. Methods"},{"key":"B133","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1038\/nrn3469","article-title":"Corticostriatal connectivity and its role in disease.","volume":"14","author":"Shepherd","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"B134","doi-asserted-by":"publisher","first-page":"779.e","DOI":"10.1016\/j.neuron.2017.07.035","article-title":"Human astrocyte maturation captured in 3D cerebral corticalspheroids derived from pluripotent stem cells.","volume":"95","author":"Sloan","year":"2017","journal-title":"Neuron"},{"key":"B135","doi-asserted-by":"publisher","first-page":"2062","DOI":"10.1038\/s41596-018-0032-7","article-title":"Generation and assembly of human brain region-specific three-dimensional cultures.","volume":"13","author":"Sloan","year":"2018","journal-title":"Nat. Protoc."},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-019-0078-4","article-title":"Modeling Parkinson\u2019s disease in midbrain-like organoids.","volume":"5","author":"Smits","year":"2019","journal-title":"NPJ Parkinson\u2019s Dis."},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-47444-6","article-title":"Functionalization of brain region-specific spheroids with isogenic microglia-like cells.","volume":"9","author":"Song","year":"","journal-title":"Sci. Rep."},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-42439-9","article-title":"Assembly of human stem cell-derived cortical spheroids and vascular spheroids to model 3-D Brain-like Tissues.","volume":"9","author":"Song","year":"","journal-title":"Sci. Rep."},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-017-0054-x","article-title":"Cerebral organoids reveal early cortical maldevelopment in schizophrenia\u2014computational anatomy and genomics, role of FGFR1.","volume":"7","author":"Stachowiak","year":"2017","journal-title":"Transl. Psychiatry"},{"key":"B140","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.neuropharm.2013.05.046","article-title":"Amygdala and bed nucleus of the stria terminalis circuitry: Implications for addiction-related behaviors.","volume":"76","author":"Stamatakis","year":"2014","journal-title":"Neuropharmacology"},{"key":"B141","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/s11065-010-9148-4","article-title":"The basics of brain development.","volume":"20","author":"Stiles","year":"2010","journal-title":"Neuropsychol. Rev."},{"key":"B142","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature10637","article-title":"Self-formation of functional adenohypophysis in three-dimensional culture.","volume":"480","author":"Suga","year":"2011","journal-title":"Nature"},{"key":"B143","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/s00441-018-2880-4","article-title":"Application of pluripotent stem cells for treatment of human neuroendocrine disorders.","volume":"375","author":"Suga","year":"2019","journal-title":"Cell Tissue Res."},{"key":"B144","doi-asserted-by":"publisher","first-page":"3138","DOI":"10.1242\/dev.120568","article-title":"Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells.","volume":"142","author":"Suzuki","year":"2015","journal-title":"Development (Cambridge, England)"},{"key":"B145","doi-asserted-by":"crossref","first-page":"4835","DOI":"10.1242\/dev.125.23.4835","article-title":"Formation of Rathke\u2019s pouch requires dual induction from the diencephalon.","volume":"125","author":"Takuma","year":"1998","journal-title":"Development"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1038\/stemcells.2009.90","article-title":"Stem cell: what\u2019s in a name?","author":"Tajbakhsh","year":"2009","journal-title":"Nat. Rep. Stem Cells"},{"key":"B147","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/s41586-019-1289-x","article-title":"Individual brain organoids reproducibly form cell diversity of the human cerebral cortex.","volume":"570","author":"Velasco","year":"2019","journal-title":"Nature"},{"key":"B148","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1146\/annurev-neuro-070918-050154","article-title":"3D Brain Organoids: Studying Brain Development and Disease outside the Embryo.","volume":"43","author":"Velasco","year":"2020","journal-title":"Annual review of neuroscience"},{"key":"B149","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1242\/dev.129.4.983","article-title":"The specification of noradrenergic locus coeruleus (LC) neurons depends on bone morphogenetic proteins (BMPs).","volume":"129","author":"Vogel-H\u00f6pker","year":"2002","journal-title":"Development (Cambridge, England)"},{"key":"B150","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.tins.2018.01.010","article-title":"Long road to ruin: noradrenergic dysfunction in neurodegenerative disease.","volume":"41","author":"Weinshenker","year":"2018","journal-title":"Trends Neurosci."},{"key":"B151","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.stem.2017.07.007","article-title":"Fusion of regionally specified HPSC-derived organoids models human brain developmentand interneuron migration.","volume":"21","author":"Xiang","year":"2017","journal-title":"Cell Stem Cell"},{"key":"B152","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.stem.2018.12.015","article-title":"hESC derived thalamic organoids form reciprocal projections when fused with cortical organoids.","volume":"24","author":"Xiang","year":"2019","journal-title":"Cell Stem Cell"},{"key":"B153","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1242\/dev.139055","article-title":"Development of the hypothalamus: conservation, modification and innovation.","volume":"144","author":"Xie","year":"2017","journal-title":"Development"},{"key":"B154","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41592-018-0255-0","article-title":"Reliability of human cortical organoid generation.","volume":"16","author":"Yoon","year":"2019","journal-title":"Nat. Methods"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1165-5","article-title":"Stem cells: past, present, and future.","volume":"10","author":"Zakrzewski","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"B156","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1038\/nbt1201-1129","article-title":"In vitro differentiation of transplantable neural precursors from human embryonic stem cells.","volume":"19","author":"Zhang","year":"2001","journal-title":"Nat. Biotechnol."},{"key":"B157","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1152\/physrev.00006.2006","article-title":"Molecular physiology of pituitary development: signalling and transcriptional networks.","volume":"87","author":"Zhu","year":"2007","journal-title":"Physiol. Rev."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.621970\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T09:18:34Z","timestamp":1623316714000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.621970\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,10]]},"references-count":157,"alternative-id":["10.3389\/fphys.2021.621970"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2021.621970","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,10]]},"article-number":"621970"}}