{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:34:22Z","timestamp":1760402062267,"version":"build-2065373602"},"reference-count":140,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T00:00:00Z","timestamp":1617408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04565\/2020","PD\/BD\/128373\/2017"],"award-info":[{"award-number":["UIDB\/04565\/2020","PD\/BD\/128373\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Among many different roles, MeCP2 has a high phenotypic impact during the different stages of brain development. Thus, it is essential to intensively investigate the function of MeCP2, and its regulated targets, to better understand the mechanisms of the disease and inspire the development of possible therapeutic strategies. Several animal models have greatly contributed to these studies, but more recently human pluripotent stem cells (hPSCs) have been providing a promising alternative for the study of RTT. The rapid evolution in the field of hPSC culture allowed first the development of 2D-based neuronal differentiation protocols, and more recently the generation of 3D human brain organoid models, a more complex approach that better recapitulates human neurodevelopment in vitro. Modeling RTT using these culture platforms, either with patient-specific human induced pluripotent stem cells (hiPSCs) or genetically-modified hPSCs, has certainly contributed to a better understanding of the onset of RTT and the disease phenotype, ultimately allowing the development of high throughput drugs screening tests for potential clinical translation. In this review, we first provide a brief summary of the main neurological features of RTT and the impact of MeCP2 mutations in the neuropathophysiology of this disease. Then, we provide a thorough revision of the more recent advances and future prospects of RTT modeling with human neural cells derived from hPSCs, obtained using both 2D and organoids culture systems, and its contribution for the current and future clinical trials for RTT.<\/jats:p>","DOI":"10.3390\/ijms22073751","type":"journal-article","created":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T22:03:36Z","timestamp":1617487416000},"page":"3751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Modeling Rett Syndrome with Human Pluripotent Stem Cells: Mechanistic Outcomes and Future Clinical Perspectives"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0655-1423","authenticated-orcid":false,"given":"Ana Rita","family":"Gomes","sequence":"first","affiliation":[{"name":"Department of Bioengineering and IBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Instituto de Medicina Molecular-Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4651-2832","authenticated-orcid":false,"given":"Tiago G.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and IBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2405-5845","authenticated-orcid":false,"given":"Joaquim M.S.","family":"Cabral","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and IBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6270-4455","authenticated-orcid":false,"given":"Maria Margarida","family":"Diogo","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and IBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1007\/s10803-015-2519-1","article-title":"Brief Report: Systematic Review of Rett Syndrome in Males","volume":"45","author":"Reichow","year":"2015","journal-title":"J. Autism Dev. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.neuron.2007.10.001","article-title":"The Story of Rett Syndrome: From Clinic to Neurobiology","volume":"56","author":"Chahrour","year":"2007","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1086\/302690","article-title":"Rett Syndrome and Beyond: Recurrent Spontaneous and Familial MECP2 Mutations at CpG Hotspots","volume":"65","author":"Wan","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_4","first-page":"1","article-title":"MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2","volume":"12","author":"Khajavi","year":"2019","journal-title":"Epigenetics Chromatin"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1093\/hmg\/9.7.1119","article-title":"Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: Correlation of disease severity with mutation type and location","volume":"9","author":"Cheadle","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1212\/01.wnl.0000291011.54508.aa","article-title":"Specific mutations in Methyl-CpG-Binding Protein 2 confer different severity in Rett syndrome","volume":"70","author":"Neul","year":"2008","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Caffarelli, C., Gonnelli, S., Pitinca, M.D.T., Camarri, S., Al Refaie, A., Hayek, J., and Nuti, R. (2020). Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with bone disease severity in Rett syndrome. BMC Med. Genet., 21.","DOI":"10.1186\/s12881-020-0960-2"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1136\/jmedgenet-2013-102113","article-title":"Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with disease severity in rett syndrome","volume":"51","author":"Cuddapah","year":"2014","journal-title":"J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/mrdd.10026","article-title":"Associations between MeCP2 mutations, X-chromosome inactivation, and phenotype","volume":"8","author":"Hoffbuhr","year":"2002","journal-title":"Ment. Retard. Dev. Disabil. Res. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0387-7604(01)00344-8","article-title":"The role of different X-inactivation pattern on the variable clinical phenotype with Rett syndrome","volume":"23","author":"Ishii","year":"2001","journal-title":"Brain Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0387-7604(12)80194-X","article-title":"Patterns of X Chromosome Inactivation in the Rett Syndrome","volume":"12","author":"Zoghbi","year":"1990","journal-title":"Brain Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/ajmg.10557","article-title":"Balanced X chromosome inactivation patterns in the Rett syndrome brain","volume":"111","author":"Shahbazian","year":"2002","journal-title":"Am. J. Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"146644","DOI":"10.1016\/j.brainres.2019.146644","article-title":"Sex differences in Mecp2 -mutant Rett syndrome model mice and the impact of cellular mosaicism in phenotype development","volume":"1729","author":"Ribeiro","year":"2020","journal-title":"Brain Res."},{"key":"ref_14","first-page":"723","article-title":"On a unusual brain atrophy syndrome in hyperammonemia in childhood","volume":"116","author":"Wochenschr","year":"1996","journal-title":"Wien. Med. Wochenschr."},{"key":"ref_15","first-page":"185","article-title":"Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2","volume":"23","author":"Amir","year":"1999","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/sj.ejhg.5201451","article-title":"Early onset seizures and Rett-like features associated with mutations in CDKL5","volume":"13","author":"Evans","year":"2005","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1136\/jmg.2009.067355","article-title":"Phenotypic variability in Rett syndrome associated with FOXG1 mutations in females","volume":"47","author":"Philippe","year":"2010","journal-title":"Med. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.neubiorev.2019.05.013","article-title":"De Rett syndrome before regression: A time window of overlooked opportunities for diagnosis and intervention","volume":"107","author":"Cosentino","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/cge.12063","article-title":"Aging in Rett syndrome: A longitudinal study","volume":"84","author":"Halbach","year":"2013","journal-title":"Clin. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.pediatrneurol.2017.01.032","article-title":"Scoliosis in Rett Syndrome: Progression, Comorbidities, and Predictors","volume":"70","author":"Killian","year":"2017","journal-title":"Pediatr. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/mds.21276","article-title":"Rett Syndrome: An Overlooked Diagnosis in Women with Stereotypic Hand Movements, Psychomotor Retardation, Parkinsonism, and Dystonia?","volume":"22","author":"Roze","year":"2007","journal-title":"Mov. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.pediatrneurol.2015.06.003","article-title":"The Changing Face of Survival in Rett Syndrome and MECP2 -Related Disorders","volume":"53","author":"Tarquinio","year":"2015","journal-title":"Pediatr. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1093\/hmg\/9.9.1369","article-title":"Rett syndrome: Analysis of MECP2 and clinical characterization of 31 patients","volume":"9","author":"Huppke","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2214\/ajr.159.1.1609693","article-title":"Cerebellar and Cerebral Abnormalities in Rett Syndrome: A Quantitative MR Analysis","volume":"159","author":"Murakami","year":"1992","journal-title":"Ajr. Am. J. Roentgenol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.seizure.2011.06.010","article-title":"Epilepsy in Rett syndrome: Association between phenotype and genotype, and implications for practice","volume":"20","author":"Cardoza","year":"2011","journal-title":"Seizure"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1212\/WNL.0b013e3181d6b852","article-title":"Epilepsy and the natural history of Rett syndrome","volume":"74","author":"Glaze","year":"2010","journal-title":"Neurology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1212\/01.wnl.0000304086.75913.b2","article-title":"The p. Val66Met polymorphism in the BDNF gene protects against early seizures in Rett syndrome","volume":"70","author":"Nectoux","year":"2008","journal-title":"Neurology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1212\/01.wnl.0000345664.72220.6a","article-title":"The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome","volume":"72","author":"Leonard","year":"2009","journal-title":"Neurology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1016\/j.clinph.2008.08.015","article-title":"Drug-resistant epilepsy and epileptic phenotype-EEG association in MECP2 mutated Rett syndrome","volume":"119","author":"Buoni","year":"2008","journal-title":"Clin. Neurophysiol."},{"key":"ref_30","first-page":"925","article-title":"Management of epilepsy in patients with Rett syndrome: Perspectives and considerations","volume":"11","author":"Krajnc","year":"2015","journal-title":"Clin. Risk Manag."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1055\/s-2002-23598","article-title":"MECP2 Mutation in a Boy with Severe Neonatal Encephalopathy: Clinical, Neuropathological and Molecular Findings","volume":"33","author":"Geerdink","year":"2002","journal-title":"Neuropediatrics"},{"key":"ref_32","first-page":"3","article-title":"MECP2 Mutations or Polymorphisms in Mentally Retarded Boys","volume":"7","author":"Bourdon","year":"2003","journal-title":"Mol. Diagn."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/ajmg.b.32707","article-title":"The array of clinical phenotypes of males with mutations in Methyl-CpG binding protein 2","volume":"180","author":"Neul","year":"2019","journal-title":"Am. J. Med. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1055\/s-2001-16620","article-title":"Rett Syndrome in a Boy with a 47, XXY Karyotype Confirmed by a Rare Mutation in the MECP2 Gene","volume":"32","author":"Schwartzman","year":"2001","journal-title":"Neuropediatrics"},{"key":"ref_35","first-page":"2","article-title":"Genomic mosaicism in the pathogenesis and inheritance of a Rett syndrome cohort","volume":"21","author":"Zhang","year":"2019","journal-title":"Genet. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.braindev.2010.09.012","article-title":"Somatic mosaicism for Y120X mutation in the MECP2 gene causes atypical Rett syndrome in a male","volume":"33","author":"Pieras","year":"2011","journal-title":"Brain Dev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1086\/444549","article-title":"Duplication of the MECP2 Region Is a Frequent Cause of Severe Mental Retardation and Progressive Neurological Symptoms in Males","volume":"77","author":"Bauters","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1097\/01.gim.0000250502.28516.3c","article-title":"Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males","volume":"8","author":"Gaudio","year":"2006","journal-title":"Genet. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1136\/jmedgenet-2017-104956","article-title":"Further delineation of the MECP2 duplication syndrome phenotype in 59 French male patients, with a particular focus on morphological and neurological features","volume":"55","author":"Miguet","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1007\/s12264-020-00467-w","article-title":"Reversal of Social Recognition Deficit in Adult Mice with MECP2 Duplication via Normalization of MeCP2 in the Medial Prefrontal Cortex","volume":"36","author":"Yu","year":"2020","journal-title":"Neurosci. Bull."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/mp.2015.128","article-title":"Altered neuronal network and rescue in a human MECP2 duplication model","volume":"21","author":"Nageshappa","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s12017-014-8295-9","article-title":"Rett Syndrome and MeCP2","volume":"16","author":"Liyanage","year":"2014","journal-title":"Neuromol. Med"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13023-016-0545-5","article-title":"Rett syndrome\u2014Biological pathways leading from MECP2 to disorder phenotypes","volume":"11","author":"Ehrhart","year":"2016","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.tins.2017.11.005","article-title":"MeCP2 as an activator of gene expression","volume":"41","author":"Horvath","year":"2019","journal-title":"Trends Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.conb.2019.04.004","article-title":"MeCP2: An epigenetic regulator of critical periods","volume":"59","author":"Picard","year":"2019","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/j.jmb.2019.10.004","article-title":"The Molecular Basis of MeCP2 Function in the Brain","volume":"432","author":"Tillotson","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Pejhan, S., and Rastegar, M. (2021). Role of dna methyl-cpg-binding protein mecp2 in rett syndrome pathobiology and mechanism of disease. Biomolecules, 11.","DOI":"10.3390\/biom11010075"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4886","DOI":"10.1093\/nar\/21.21.4886","article-title":"Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2","volume":"21","author":"Nan","year":"1993","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/30764","article-title":"Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex","volume":"393","author":"Nan","year":"1998","journal-title":"Lett. Nat."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lagger, S., Connelly, J.C., Schweikert, G., Webb, S., Selfridge, J., Ramsahoye, B.H., Yu, M., He, C., Sanguinetti, G., and Sowers, L.C. (2017). MeCP2 recognizes cytosine methylated tri- nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006793"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"34115","DOI":"10.1074\/jbc.M105747200","article-title":"The Ski Protein Family Is Required for MeCP2-mediated Transcriptional Repression","volume":"276","author":"Kokura","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/nn.3434","article-title":"Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR\/SMRT co-repressor","volume":"16","author":"Lyst","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.molcel.2019.10.032","article-title":"MeCP2 Represses the Rate of Transcriptional Initiation of Highly Methylated Long Genes","volume":"77","author":"Boxer","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.1073\/pnas.1505909112","article-title":"MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome","volume":"112","author":"Chen","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6800","DOI":"10.1073\/pnas.1411269112","article-title":"Reading the unique DNA methylation landscape of the and MeCP2","volume":"112","author":"Kinde","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nature14319","article-title":"Disruption of DNA-methylation-dependent long gene repression in Rett syndrome","volume":"522","author":"Gabel","year":"2015","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.molcel.2019.10.033","article-title":"MeCP2 Represses Enhancers through Chromosome Article MeCP2 Represses Enhancers through","volume":"77","author":"Clemens","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1126\/science.1153252","article-title":"MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription","volume":"320","author":"Chahrour","year":"2008","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8746","DOI":"10.1523\/JNEUROSCI.1281-19.2020","article-title":"MeCP2 Levels Regulate the 3D Structure of Heterochromatic Foci in Mouse Neurons","volume":"40","author":"Baker","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.cell.2013.01.038","article-title":"An AT-Hook Domain in MeCP2 Determines the Clinical Course of Rett Syndrome and Related Disorders","volume":"152","author":"Baker","year":"2013","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1002\/jcb.21582","article-title":"A case report: Bone marrow mesenchymal stem cells from a rett syndrome patient are prone to senescence and show a lower degree of apoptosis","volume":"103","author":"Squillaro","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Squillaro, T., Alessio, N., Capasso, S., Di Bernardo, G., Melone, M.A.B., Peluso, G., and Galderisi, U. (2019). Senescence phenomena and metabolic alteration in mesenchymal stromal cells from a mouse model of rett syndrome. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102508"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/s41583-018-0006-3","article-title":"Rett syndrome: Insights into genetic, molecular and circuit mechanisms","volume":"19","author":"Ip","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1006\/nbdi.2001.0428","article-title":"Gene expression profiling in postmortem Rett Syndrome brain: Differential gene expression and patient classification","volume":"8","author":"Colantuoni","year":"2001","journal-title":"Neurobiol. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"101533","DOI":"10.1016\/j.scr.2019.101533","article-title":"Generation of four H1 hESC sublines carrying a hemizygous knock-out\/mutant MECP2","volume":"40","author":"Zeng","year":"2019","journal-title":"Stem Cell Res."},{"key":"ref_66","first-page":"1","article-title":"Efficient and Precise CRISPR\/Cas9- Mediated MECP2 Modifications in Human-Induced Pluripotent Stem Cells","volume":"10","author":"Thanh","year":"2019","journal-title":"Front. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.stem.2010.06.024","article-title":"Female human iPS cells retain inactive X-chromosome","volume":"7","author":"Tchieu","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fpsyt.2012.00024","article-title":"X-chromosome inactivation in Rett syndrome human induced pluripotent stem cells","volume":"3","author":"Cheung","year":"2012","journal-title":"Front. Psychiatry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.celrep.2019.03.019","article-title":"Global Characterization of X Chromosome Report Global Characterization of X Chromosome Inactivation in Human Pluripotent Stem Cells","volume":"27","author":"Bar","year":"2019","journal-title":"Cell Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.cell.2010.10.016","article-title":"A Model for Neural Development and Treatment of Rett Syndrome Using Human Induced Pluripotent Stem Cells","volume":"143","author":"Marchetto","year":"2010","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Ananiev, G., Williams, E.C., Li, H., and Chang, Q. (2011). Isogenic Pairs of Wild Type and Mutant Induced Pluripotent Stem Cell ( iPSC ) Lines from Rett Syndrome Patients as In Vitro Disease Model. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025255"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"14169","DOI":"10.1073\/pnas.1018979108","article-title":"Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome","volume":"108","author":"Kim","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.nbd.2015.01.001","article-title":"MECP2e1 isoform mutation affects the form and function of neurons from Rett syndrome patient iPS cells","volume":"76","author":"Djuric","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nbt.1529","article-title":"Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling","volume":"27","author":"Chambers","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1002\/biot.201400751","article-title":"Neural commitment of human pluripotent stem cells under defined conditions recapitulates neural development and generates patient-specific neural cells","volume":"10","author":"Fernandes","year":"2015","journal-title":"Biotechnol. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/s12017-016-8421-y","article-title":"Choline Ameliorates Disease Phenotypes in Human iPSC Models of Rett Syndrome","volume":"18","author":"Chin","year":"2016","journal-title":"Neuromol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1523\/JNEUROSCI.3735-16.2017","article-title":"CREB signaling is involved in rett syndrome pathogenesis","volume":"37","author":"Bu","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.bbrc.2017.10.073","article-title":"The L1 adhesion molecule normalizes neuritogenesis in Rett syndrome-derived neural precursor cells","volume":"494","author":"Yoo","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1073\/pnas.1524013113","article-title":"KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome","volume":"113","author":"Tang","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1126\/scitranslmed.aau0164","article-title":"Pharmacological enhancement of KCC2 gene expression exerts therapeutic effects on human Rett syndrome neurons and Mecp2 mutant mice","volume":"11","author":"Tang","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/j.stemcr.2018.04.001","article-title":"Loss of MECP2 Leads to Activation of P53 and Neuronal Senescence","volume":"10","author":"Ohashi","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.yexcr.2018.05.001","article-title":"iPSC-derived neurons profi ling reveals GABAergic circuit disruption and acetylated \u03b1 -tubulin defect which improves after iHDAC6 treatment in Rett syndrome","volume":"368","author":"Landucci","year":"2018","journal-title":"Exp. Cell Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.molcel.2020.05.016","article-title":"Dysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons","volume":"79","author":"Xiang","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_84","first-page":"1","article-title":"Quantitative proteomic analysis of Rett iPSC-derived neuronal progenitors","volume":"3","author":"Hinz","year":"2020","journal-title":"Mol. Autism"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"16086","DOI":"10.1073\/pnas.1902513116","article-title":"Exosomes regulate neurogenesis and circuit assembly","volume":"116","author":"Sharma","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Chen, X., Han, X., Blanchi, B., Guan, W., Ge, W., Yu, Y., and Sun, Y.E. (2020). Graded and pan-neural disease phenotypes of Rett Syndrome linked with dosage of functional MeCP2. Protein Cell, 1\u201314.","DOI":"10.1007\/s13238-020-00773-z"},{"key":"ref_87","first-page":"1","article-title":"Brain Organoids: Human Neurodevelopment in a Dish","volume":"12","author":"Lancaster","year":"2020","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e12523","DOI":"10.15252\/emmm.202012523","article-title":"Pharmacological reversal of synaptic and network pathology in human MECP 2 -KO neurons and cortical organoids","volume":"13","author":"Trujillo","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_89","doi-asserted-by":"crossref","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":"ref_90","doi-asserted-by":"crossref","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":"ref_91","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/nmeth.4304","article-title":"Fused cerebral organoids model interactions between brain regions","volume":"12","author":"Bagley","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/nbt.3777","article-title":"Combined small-molecule inhibition accelerates the derivation of functional cortical neurons from human pluripotent stem cells","volume":"35","author":"Qi","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1073\/pnas.1521255113","article-title":"Layered hydrogels accelerate iPSC-derived neuronal maturation and reveal migration defects caused by MeCP2 dysfunction","volume":"113","author":"Zhang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1088\/1748-605X\/aaaf2b","article-title":"Human Rett-derived neuronal progenitor cells in 3D graphene scaffold as an in vitro platform to study the effect of electrical stimulation on neuronal differentiation","volume":"13","author":"Nguyen","year":"2018","journal-title":"Biomed. Mater."},{"key":"ref_95","doi-asserted-by":"crossref","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":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcell.2020.610427","article-title":"Modeling Rett Syndrome With Human Patient-Specific Forebrain Organoids","volume":"8","author":"Gomes","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.stem.2013.09.001","article-title":"Global Transcriptional and Translational Repression in Human-Embryonic-Stem-Cell-Derived Rett Syndrome Neurons","volume":"13","author":"Kwok","year":"2013","journal-title":"Cell Stem Cell."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1073\/pnas.0812394106","article-title":"Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice","volume":"106","author":"Tropea","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"9941","DOI":"10.1073\/pnas.1311685111","article-title":"Functional recovery with recombinant human IGF1 treatment in a mouse model of Rett Syndrome","volume":"111","author":"Castro","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4596","DOI":"10.1073\/pnas.1311141111","article-title":"Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome","volume":"111","author":"Khwaja","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","first-page":"323","article-title":"Placebo-controlled crossover assessment of mecasermin for the treatment of Rett syndrome","volume":"5","author":"Leary","year":"2018","journal-title":"Neurology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e1912","DOI":"10.1212\/WNL.0000000000007316","article-title":"Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome","volume":"92","author":"Glaze","year":"2019","journal-title":"Neurology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep04388","article-title":"Cyclic glycine-proline regulates IGF-1 homeostasis by altering the binding of IGFBP-3 to IGF-1","volume":"4","author":"Guan","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"101935","DOI":"10.1016\/j.npep.2019.05.006","article-title":"Cyclic glycine-proline administration normalizes high-fat diet-induced synaptophysin expression in obese rats","volume":"76","author":"Li","year":"2019","journal-title":"Neuropeptides"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Devesa, J., Devesa, O., Carrillo, M., Casteleiro, N., Devesa, A., Llorente, D., and Gonz\u00e1lez, C. (2018). Rett Syndrome: Treatment with IGF-I, Melatonin, Blackcurrant Extracts, and Rehabilitation. Reports, 1.","DOI":"10.20944\/preprints201805.0300.v1"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"16981","DOI":"10.3390\/ijms160816981","article-title":"Evaluating the oxidative stress in inflammation: Role of melatonin","volume":"16","author":"Calpena","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.nbd.2014.04.006","article-title":"Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome","volume":"68","author":"Signorini","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fncel.2017.00058","article-title":"Mitochondrial dysfunction in the pathogenesis of rett syndrome: Implications for mitochondria-targeted therapies","volume":"11","author":"Shulyakova","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.pediatrneurol.2011.02.001","article-title":"Prolonged-release melatonin for children with neurodevelopmental disorders","volume":"45","author":"Zisapel","year":"2011","journal-title":"Pediatr. Neurol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s11689-018-9234-0","article-title":"Recent progress and considerations for AAV gene therapies targeting the central nervous system","volume":"10","author":"Lykken","year":"2018","journal-title":"J. Neurodev. Disord."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.tins.2015.12.008","article-title":"Rett Syndrome: Crossing the Threshold to Clinical Translation","volume":"39","author":"Katz","year":"2016","journal-title":"Trends Neurosci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1038\/s41431-020-0652-6","article-title":"AAV-mediated FOXG1 gene editing in human Rett primary cells","volume":"28","author":"Croci","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_113","first-page":"13612","article-title":"Systemic Delivery of MeCP2 Rescues Behavioral and Cellular Deficits in Female Mouse Models of Rett Syndrome","volume":"33","author":"Garg","year":"2013","journal-title":"Neurobiol. Dis. Syst."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.omtm.2017.04.007","article-title":"Development of a Novel AAV Gene Therapy Cassette with Improved Safety Features and Efficacy in a Mouse Model of Rett Syndrome","volume":"5","author":"Gadalla","year":"2017","journal-title":"Mol. Methods Clin. Dev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.omtm.2017.04.006","article-title":"Improved MECP2 Gene Therapy Extends the Survival of MeCP2-Null Mice without Apparent Toxicity after Intracisternal Delivery","volume":"5","author":"Sinnett","year":"2017","journal-title":"Mol. Methods Clin. Dev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1038\/nn2010","article-title":"Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA","volume":"10","author":"Klein","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_117","first-page":"1","article-title":"Understanding the Modus Operandi of MicroRNA Regulatory Clusters","volume":"8","author":"Ribeiro","year":"2019","journal-title":"Cells"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.conb.2018.12.005","article-title":"Shared and derived features of cellular diversity in the human cerebral cortex","volume":"56","author":"Miller","year":"2019","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41586-019-1506-7","article-title":"Conserved cell types with divergent features in human versus mouse cortex","volume":"573","author":"Hodge","year":"2019","journal-title":"Nature"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.jns.2017.08.2711","article-title":"Sarizotan for the treatment of severe apnea in patients with rett syndrome (RTT): Rationale and design of international 6-month, randomized, placebo-controlled phase III trial (STARs)","volume":"381","author":"Anand","year":"2017","journal-title":"J. Neurol. Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1165\/rcmb.2013-0372OC","article-title":"Effect of Sarizotan, a 5-HT 1a and D2-Like Receptor Agonist, on Respiration in Three Mouse Models of Rett Syndrome","volume":"50","author":"Abdala","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1016\/j.celrep.2016.12.001","article-title":"Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain Resource Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain","volume":"17","author":"Luo","year":"2016","journal-title":"Cell Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1038\/s41593-020-00730-3","article-title":"Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo","volume":"23","author":"Chiaradia","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_124","doi-asserted-by":"crossref","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":"ref_125","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.semcdb.2020.05.025","article-title":"Bioengineering tissue morphogenesis and function in human neural organoids","volume":"111","author":"Fedorchak","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_126","first-page":"1","article-title":"Brain organoids: Advances, applications and challenges","volume":"146","author":"Qian","year":"2019","journal-title":"Co. Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/nbt.3906","article-title":"Guided self-organization and cortical plate formation in human brain organoids","volume":"35","author":"Lancaster","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_128","doi-asserted-by":"crossref","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":"ref_129","first-page":"383","article-title":"Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration Resource Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development","volume":"21","author":"Xiang","year":"2017","journal-title":"Stem Cell"},{"key":"ref_130","doi-asserted-by":"crossref","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":"ref_131","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.3389\/fbioe.2020.00070","article-title":"Maturation of human pluripotent stem cell-derived cerebellar neurons in the absence of co-culture","volume":"8","author":"Silva","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Nayler, S., Agarwal, D., Curion, F., Bowden, R., and Becker, E.B.E. (2020). Single-cell sequencing of human iPSC-derived cerebellar organoids shows recapitulation of cerebellar development. bioRxiv, 1\u201330.","DOI":"10.1101\/2020.07.01.182196"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"101870","DOI":"10.1016\/j.scr.2020.101870","article-title":"Reproducible generation of human midbrain organoids for in vitro modeling of Parkinson \u2019 s disease","volume":"46","author":"Louise","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s00441-020-03249-y","article-title":"Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids","volume":"382","author":"Smits","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_135","first-page":"1","article-title":"Three-dimensional induction of dorsal, intermediate and ventral spinal cord tissues from human pluripotent stem cells","volume":"145","author":"Ogura","year":"2018","journal-title":"Co. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nature22330","article-title":"Assembly of functionally integrated human forebrain spheroids","volume":"545","author":"Birey","year":"2017","journal-title":"Nature"},{"key":"ref_137","first-page":"565","article-title":"Generation of human brain region\u2014Specific organoids using a miniaturized spinning bioreactor","volume":"13","author":"Qian","year":"2018","journal-title":"Nature"},{"key":"ref_138","first-page":"1","article-title":"Scalable Generation of Mature Cerebellar Organoids from Human Pluripotent Stem Cells and Characterization by Immunostaining","volume":"160","author":"Silva","year":"2020","journal-title":"JOVE"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Shi, Y., Sun, L., Id, M.W., Id, J.L., Id, S.Z., Li, R., Li, P., Guo, L., Fang, A., and Id, R.C. (2020). Vascularized human cortical organoids (vOrganoids) model cortical development in vivo. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000705"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Salmon, I., Grebenyuk, S., Rahman, A., Fattah, A., Rustandi, G., Verfaillie, C., and Ranga, A. (2021). Engineering neurovascular organoids with 3D printed microfluidic chips. bioRxiv, 1\u201322.","DOI":"10.1101\/2021.01.09.425975"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3751\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:26:15Z","timestamp":1760361975000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,3]]},"references-count":140,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22073751"],"URL":"https:\/\/doi.org\/10.3390\/ijms22073751","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,4,3]]}}}