{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:59:26Z","timestamp":1788184766300,"version":"build-2803163510"},"reference-count":106,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T00:00:00Z","timestamp":1618876800000},"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. Endocrinol."],"abstract":"<jats:p>Stem cell-based therapies to reconstitute <jats:italic>in vivo<\/jats:italic> organ function hold great promise for future clinical applications to a variety of diseases. Hypothyroidism resulting from congenital lack of functional thyrocytes, surgical tissue removal, or gland ablation, represents a particularly attractive endocrine disease target that may be conceivably cured by transplantation of long-lived functional thyroid progenitors or mature follicular epithelial cells, provided a source of autologous cells can be generated and a variety of technical and biological challenges can be surmounted. Here we review the emerging literature indicating that thyroid follicular epithelial cells can now be engineered <jats:italic>in vitro<\/jats:italic> from the pluripotent stem cells (PSCs) of mice, normal humans, or patients with congenital hypothyroidism. We review the <jats:italic>in vivo<\/jats:italic> embryonic development of the thyroid gland and explain how emerging discoveries in developmental biology have been utilized as a roadmap for driving PSCs, which resemble cells of the early embryo, into mature functional thyroid follicles <jats:italic>in vitro<\/jats:italic>. Finally, we discuss the bioengineering, biological, and clinical hurdles that now need to be addressed if the goals of life-long cure of hypothyroidism through cell- and\/or gene-based therapies are to be attained.<\/jats:p>","DOI":"10.3389\/fendo.2021.666565","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T21:43:25Z","timestamp":1618955005000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Derivation of Thyroid Follicular Cells From Pluripotent Stem Cells: Insights From Development and Implications for Regenerative Medicine"],"prefix":"10.3389","volume":"12","author":[{"given":"Alberto","family":"Posabella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea B.","family":"Alber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik J.","family":"Undeutsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul A.","family":"Droeser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony N.","family":"Hollenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laertis","family":"Ikonomou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrell N.","family":"Kotton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.10.008","article-title":"Pluripotency and Cellular Reprogramming: Facts, Hypotheses, Unresolved Issues","volume":"143","author":"Hanna","year":"2010","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/292154a0","article-title":"Establishment in Culture of Pluripotential Cells from Mouse Embryoske","volume":"292","author":"Evans","year":"1981","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5391.1145","article-title":"Embryonic stem cell lines derived from human blastocysts","volume":"282","author":"Thomson","year":"1998","journal-title":"Science"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nri934","article-title":"Stem cell medicine encounters the immune system","volume":"2","author":"Bradley","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.142298299","article-title":"Characterization of the expression of MHC proteins in human embryonic stem cells","volume":"99","author":"Drukker","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"B6","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s00441-007-0486-3","article-title":"Immunogenicity of human embryonic stem cells","volume":"331","author":"Grinnemo","year":"2008","journal-title":"Cell Tissue Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.02.008","article-title":"Differentiation of embryonic stem cells to clinically relevant populations: Lessons from embryonic development","volume":"132","author":"Murry","year":"2008","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nature10135","article-title":"Immunogenicity of induced pluripotent stem cells","volume":"474","author":"Zhao","year":"2011","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1126\/science.1151526","article-title":"Induced pluripotent stem cell lines derived from human somatic cells","volume":"318","author":"Yu","year":"2007","journal-title":"Science"},{"key":"B12","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/ncb0511-497d","article-title":"Harnessing the potential of induced pluripotent stem cells for regenerative medicine","volume":"13","author":"Wu","year":"2011","journal-title":"Nat Cell Biol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.38","article-title":"The Use of Induced Pluripotent Stem Cells in Drug Development","volume":"89","author":"Inoue","year":"2011","journal-title":"Clin Pharmacol Ther"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.09.004","article-title":"Regeneration of Thyroid Function by Transplantation of Differentiated Pluripotent Stem Cells","volume":"17","author":"Kurmann","year":"2015","journal-title":"Cell Stem Cell"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2020.06.006","article-title":"A Highly Phenotyped Open Access Repository of Alpha-1 Antitrypsin Deficiency Pluripotent Stem Cells","volume":"15","author":"Kaserman","year":"2020","journal-title":"Stem Cell Rep"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1080\/13506129.2018.1489228","article-title":"A library of ATTR amyloidosis patient-specific induced pluripotent stem cells for disease modelling and in vitro testing of novel therapeutics","volume":"25","author":"Giadone","year":"2018","journal-title":"Amyloid J Protein Fold Disord"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2020.102036","article-title":"The Global Alliance for iPSC Therapies (GAiT)","volume":"49","author":"Sullivan","year":"2020","journal-title":"Stem Cell Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.01.010","article-title":"Induced Pluripotent Stem Cell Differentiation Enables Functional Validation of GWAS Variants in Metabolic Disease","volume":"20","author":"Warren","year":"2017","journal-title":"Cell Stem Cell"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1242\/dev.145615","article-title":"Development of the thyroid gland","volume":"144","author":"Nilsson","year":"2017","journal-title":"Development"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s004270050170","article-title":"Demarcation of ventral territories by the homeobox gene NKX2.1 during early chick development","volume":"208","author":"Pera","year":"1998","journal-title":"Dev Genes Evol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.mce.2009.05.011","article-title":"Thyroid gland development and function in the zebrafish model","volume":"312","author":"Porazzi","year":"2009","journal-title":"Mol Cell Endocrinol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/0955-0674(95)80071-9","article-title":"In-Vitro Differentiation of Embryonic Stem-Cells","volume":"7","author":"Keller","year":"1995","journal-title":"Curr Opin Cell Biol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24771","article-title":"Derivation of Endodermal Progenitors From Pluripotent Stem Cells","volume":"230","author":"Ikonomou","year":"2015","journal-title":"J Cell Physiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.mod.2005.10.001","article-title":"FGF signaling is necessary for establishing gut tube domains along the anterior-posterior axis in vivo","volume":"123","author":"Dessimoz","year":"2006","journal-title":"Mech Dev"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1242\/dev.001230","article-title":"Repression of Wnt\/beta-catenin signaling in the anterior endoderm is essential for liver and pancreas development","volume":"134","author":"McLin","year":"2007","journal-title":"Development"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.042308.113344","article-title":"Vertebrate Endoderm Development and Organ Formation","volume":"25","author":"Zorn","year":"2009","journal-title":"Annu Rev Cell Dev Biol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2005.06.009","article-title":"Germ layer induction from embryonic stem cells","volume":"33","author":"Gadue","year":"2005","journal-title":"Exp Hematol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/s1534-5807(02)00321-0","article-title":"Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks","volume":"3","author":"Perea-Gomez","year":"2002","journal-title":"Dev Cell"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1258","article-title":"BMP-4 is required for hepatic specification of mouse embryonic stem cell-derived definitive endoderm","volume":"24","author":"Gouon-Evans","year":"2006","journal-title":"Nat Biotechnol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01044","article-title":"Development of definitive endoderm from embryonic stem cells in culture","volume":"131","author":"Kubo","year":"2004","journal-title":"Development"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603916103","article-title":"Wnt and TGF-beta signaling are required for the induction of an in vitro model of primitive streak formation using embryonic stem cells","volume":"103","author":"Gadue","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1163","article-title":"Efficient differentiation of human embryonic stem cells to definitive endoderm","volume":"23","author":"D\u2019Amour","year":"2005","journal-title":"Nat Biotechnol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43853","article-title":"and iPS cells can form similar definitive endoderm despite differences in imprinted genes","volume":"121","author":"Christodoulou","year":"2011","journal-title":"J Clin Invest"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1788","article-title":"Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells","volume":"29","author":"Green","year":"2011","journal-title":"Nat Biotechnol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.stem.2012.01.019","article-title":"Efficient Derivation of Purified Lung and Thyroid Progenitors from Embryonic Stem Cells","volume":"10","author":"Longmire","year":"2012","journal-title":"Cell Stem Cell"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003-0028","article-title":"Thyroid development and its disorders: Genetics and molecular mechanisms","volume":"25","author":"De Felice","year":"2004","journal-title":"Endocr Rev"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02872","article-title":"Early developmental specification of the thyroid gland depends on han-expressing surrounding tissue and on FGF signals","volume":"134","author":"Wendl","year":"2007","journal-title":"Development"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1677\/jme-10-0084","article-title":"Morphogenetics of early thyroid development","volume":"46","author":"Fagman","year":"2011","journal-title":"J Mol Endocrinol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.1.60","article-title":"The T\/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary","volume":"10","author":"Kimura","year":"1996","journal-title":"Genes Dev"},{"key":"B40","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/ng0598-87","article-title":"Follicular cells of the thyroid gland require Pax8 gene function","volume":"19","author":"Mansouri","year":"1998","journal-title":"Nat Genet"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1056\/nejm198103193041205","article-title":"Thyroid development and disorders of thyroid function in the newborn","volume":"304","author":"Fisher","year":"1981","journal-title":"N Engl J Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.160","article-title":"Detection and treatment of congenital hypothyroidism","volume":"8","author":"Gruters","year":"2012","journal-title":"Nat Rev Endocrinol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/1289","article-title":"A mouse model for hereditary thyroid dysgenesis and cleft palate","volume":"19","author":"De Felice","year":"1998","journal-title":"Nat Genet"},{"key":"B44","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/nrendo.2014.186","article-title":"Thyroid transcription factors in development, differentiation and disease","volume":"11","author":"Fern\u00e1ndez","year":"2015","journal-title":"Nat Rev Endocrinol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1007\/s00431-004-1559-x","article-title":"Brain-Thyroid-Lung syndrome: a patient with a severe multi-system disorder due to a de novo mutation in the thyroid transcription factor 1 gene","volume":"164","author":"Willemsen","year":"2005","journal-title":"Eur J Pediatr"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1172\/jc1200214341","article-title":"Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency","volume":"109","author":"Krude","year":"2002","journal-title":"J Clin Invest"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/ng0598-83","article-title":"PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis","volume":"19","author":"Macchia","year":"1998","journal-title":"Nat Genet"},{"key":"B48","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/1294","article-title":"Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia","volume":"19","author":"Clifton-Bligh","year":"1998","journal-title":"Nat Genet"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.08.048","article-title":"An integrated regulatory network controlling survival and migration in thyroid organogenesis","volume":"276","author":"Parlato","year":"2004","journal-title":"Dev Biol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-0204","article-title":"Minireview: Intrinsic and Extrinsic Factors in Thyroid Gland Development: An Update","volume":"152","author":"De Felice","year":"2011","journal-title":"Endocrinology"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20653","article-title":"The developing mouse thyroid: Embryonic vessel contacts and parenchymal growth pattern during specification, budding, migration, and lobulation","volume":"235","author":"Fagman","year":"2006","journal-title":"Dev Dyn"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.184291","article-title":"Pax8 controls thyroid follicular polarity through cadherin-16","volume":"130","author":"Koumarianou","year":"2017","journal-title":"J Cell Sci"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1242\/dev.134171","article-title":"Thyroid follicle development requires Smad1\/5-and endothelial cell-dependent basement membrane assembly","volume":"143","author":"Villacorte","year":"2016","journal-title":"Development"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034125","article-title":"The Sodium\/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications","volume":"79","author":"Ravera","year":"2017","journal-title":"Annu Rev Physiol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.mce.2017.01.038","article-title":"Thyroid hormone biosynthesis and release","volume":"458","author":"Carvalho","year":"2017","journal-title":"Mol Cell Endocrinol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.242328999","article-title":"Role of the thyroid-stimulating hormone receptor signaling in development and differentiation of the thyroid gland","volume":"99","author":"Postiglione","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-0122","article-title":"Committing embryonic stem cells to differentiate into thyrocyte-like cells in vitro","volume":"144","author":"Lin","year":"2003","journal-title":"Endocrinology"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1239","article-title":"Directed differentiation of mouse embryonic stem cells into thyroid follicular cells","volume":"147","author":"Arufe","year":"2006","journal-title":"Endocrinology"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.02.035","article-title":"Differentiation of murine embryonic stem cells to thyrocytes requires insulin and insulin-like growth factor-1","volume":"381","author":"Arufe","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"key":"B60","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.stem.2008.06.009","article-title":"Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification","volume":"3","author":"Bondue","year":"2008","journal-title":"Cell Stem Cell"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3467","article-title":"Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity","volume":"16","author":"Mazzoni","year":"2013","journal-title":"Nat Neurosci"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11208","article-title":"Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming","volume":"7","author":"Moreau","year":"2016","journal-title":"Nat Commun"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.02.016","article-title":"Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes","volume":"8","author":"Pawlowski","year":"2017","journal-title":"Stem Cell Rep"},{"key":"B64","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/nature11525","article-title":"Generation of functional thyroid from embryonic stem cells","volume":"491","author":"Antonica","year":"2012","journal-title":"Nature"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2012.0644","article-title":"Thyroid Follicle Formation and Thyroglobulin Expression in Multipotent Endodermal Stem Cells","volume":"23","author":"Ma","year":"2013","journal-title":"Thyroid"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1242\/dev.150193","article-title":"Pluripotent stem cell differentiation reveals distinct developmental pathways regulating lung- versus thyroid-lineage specification","volume":"144","author":"Serra","year":"2017","journal-title":"Development"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1172\/jci89950","article-title":"Prospective isolation of NKX2-1-expressing human lung progenitors derived from pluripotent stem cells","volume":"127","author":"Hawkins","year":"2017","journal-title":"J Clin Invest"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2014.0537","article-title":"Human Embryonic Stem Cells Form Functional Thyroid Follicles","volume":"25","author":"Ma","year":"2015","journal-title":"Thyroid"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2016.12.024","article-title":"Thyroid Progenitors Are Robustly Derived from Embryonic Stem Cells through Transient, Developmental Stage-Specific Overexpression of Nkx2-1","volume":"8","author":"Dame","year":"2017","journal-title":"Stem Cell Rep"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003734","article-title":"Epigenetic Landscapes Explain Partially Reprogrammed Cells and Identify Key Reprogramming Genes","volume":"10","author":"Lang","year":"2014","journal-title":"PloS Comput Biol"},{"key":"B71","doi-asserted-by":"publisher","first-page":"016001","DOI":"10.1088\/1478-3975\/aa90e0","article-title":"Cellular reprogramming dynamics follow a simple 1D reaction coordinate","volume":"15","author":"Pusuluri","year":"2018","journal-title":"Phys Biol"},{"key":"B72","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.stem.2019.12.009","article-title":"Reconstructed Single-Cell Fate Trajectories Define Lineage Plasticity Windows during Differentiation of Human PSC-Derived Distal Lung Progenitors","volume":"26","author":"Hurley","year":"2020","journal-title":"Cell Stem Cell"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.08.014","article-title":"Differentiation of Human Pluripotent Stem Cells into Functional Lung Alveolar Epithelial Cells","volume":"21","author":"Jacob","year":"2017","journal-title":"Cell Stem Cell"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.08.015","article-title":"Gene expression profiling at early organogenesis reveals both common and diverse mechanisms in foregut patterning","volume":"359","author":"Fagman","year":"2011","journal-title":"Dev Biol"},{"key":"B75","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/s41467-020-14348-3","article-title":"The in vivo genetic program of murine primordial lung epithelial progenitors","volume":"11","author":"Ikonomou","year":"2020","journal-title":"Nat Commun"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.07.039","article-title":"Generation of Rat Pancreas in Mouse by Interspecific Blastocyst Injection of Pluripotent Stem Cells","volume":"142","author":"Kobayashi","year":"2010","journal-title":"Cell"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0364-y","article-title":"Direct analysis of brain phenotypes via neural blastocyst complementation","volume":"15","author":"Dai","year":"2020","journal-title":"Nat Protoc"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2020.05.002","article-title":"Generation of rat blood vasculature and hematopoietic cells in rat-mouse chimeras by blastocyst complementation","volume":"47","author":"Wang","year":"2020","journal-title":"J Genet Genomics"},{"key":"B79","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/s41467-019-08394-9","article-title":"Generation of pluripotent stem cell-derived mouse kidneys in Sall1-targeted anephric rats","volume":"10","author":"Goto","year":"2019","journal-title":"Nat Commun"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0635-8","article-title":"Generation of functional lungs via conditional blastocyst complementation using pluripotent stem cells","volume":"25","author":"Mori","year":"2019","journal-title":"Nat Med"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201909-1836OC","article-title":"In Vivo Generation of Lung and Thyroid Tissues from Embryonic Stem Cells Using Blastocyst Complementation","volume":"203","author":"Wen","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.609697","article-title":"Generation of Thyroid Tissues From Embryonic Stem Cells via Blastocyst Complementation In Vivo","volume":"11","author":"Ran","year":"2020","journal-title":"Front Endocrinol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202009-3548ED","article-title":"The Coming-of-Age of Lung Generation by Blastocyst Complementation","volume":"203","author":"Ikonomou","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"B84","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1159\/000363156","article-title":"Clinical Genetics of Congenital Hypothyroidism","volume":"26","author":"Szinnai","year":"2014","journal-title":"Endocr Dev"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1159\/000363155","article-title":"Diagnosis, Treatment and Outcome of Congenital Hypothyroidism","volume":"26","author":"Van Vliet","year":"2014","journal-title":"Endocr Dev"},{"key":"B86","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.mce.2019.110638","article-title":"Defects in protein folding in congenital hypothyroidism","volume":"501","author":"Targovnik","year":"2020","journal-title":"Mol Cell Endocrinol"},{"key":"B87","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1750-1172-5-17","article-title":"Congenital hypothyroidism","volume":"5","author":"Rastogi","year":"2010","journal-title":"Orphanet J Rare Dis"},{"key":"B88","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.mce.2016.11.012","article-title":"Regenerative therapy for hypothyroidism: Mechanisms and possibilities","volume":"445","author":"Hollenberg","year":"2017","journal-title":"Mol Cell Endocrinol"},{"key":"B89","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.clp.2017.10.004","article-title":"Congenital Hypothyroidism","volume":"45","author":"Wassner","year":"2018","journal-title":"Clin Perinatol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-019-00230-w","article-title":"Evaluation and management of the child with hypothyroidism","volume":"15","author":"Leung","year":"2019","journal-title":"World J Pediatr"},{"key":"B91","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/1753-2000-6-32","article-title":"Health- related quality of life and self-worth in 10-year old children with congenital hypothyroidism diagnosed by neonatal screening","volume":"6","author":"van der Sluijs Veer","year":"2012","journal-title":"Child Adolesc Psychiatry Ment Health"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2014.0028","article-title":"Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement","volume":"24","author":"Jonklaas","year":"2014","journal-title":"Thyroid"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2002.01654.x","article-title":"Psychological well-being in patients on \u2018adequate\u2019 doses of L-thyroxine: results of a large, controlled community-based questionnaire study","volume":"57","author":"Saravanan","year":"2002","journal-title":"Clin Endocrinol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-019-02006-8","article-title":"Thyroxine and treatment of hypothyroidism: seven decades of experience","volume":"66","author":"Mateo","year":"2019","journal-title":"Endocrine"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.06.006","article-title":"Epigenomic State Transitions Characterize Tumor Progression in Mouse Lung Adenocarcinoma","volume":"38","author":"LaFave","year":"2020","journal-title":"Cancer Cell"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2020.03.006","article-title":"Bioprocess Technologies that Preserve the Quality of iPSCs","volume":"38","author":"Polanco","year":"2020","journal-title":"Trends Biotechnol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.1.472","article-title":"Suspension culture of separated follicles consisting of differentiated thyroid epithelial cells","volume":"77","author":"Nitsch","year":"1980","journal-title":"Proc Natl Acad Sci USA"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.94.2.489","article-title":"Basal Lamina Formation on Thyroid Epithelia in Separated Follicles in Suspension Culture","volume":"94","author":"Garbi","year":"1982","journal-title":"J Cell Biol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(84)90395-1","article-title":"Embedding in a Collagen Gel Stabilizes the Polarity of Epithelial-Cells in Thyroid-Follicles in Suspension-Culture","volume":"151","author":"Garbi","year":"1984","journal-title":"Exp Cell Res"},{"key":"B100","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1677\/joe.0.1310499","article-title":"Iodide uptake and organification, triiodothyronine secretion, cyclic-AMP accumulation and cell-proliferation in an optimized system of human thyroid-follicles cultured in collagen gel suspended in serum-free medium","volume":"131","author":"Kraiem","year":"1991","journal-title":"J Endocrinol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2018.0068","article-title":"Regeneration of a Bioengineered Thyroid Using Decellularized Thyroid Matrix","volume":"29","author":"Pan","year":"2019","journal-title":"Thyroid"},{"key":"B102","doi-asserted-by":"publisher","first-page":"034105","DOI":"10.1088\/1758-5090\/aa7fdd","article-title":"Bioprinting of a functional vascularized mouse thyroid gland construct","volume":"9","author":"Bulanova","year":"2017","journal-title":"Biofabrication"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2009.0119","article-title":"Tissue-Engineered Thyroid Cell Sheet Rescued Hypothyroidism in Rat Models After Receiving Total Thyroidectomy Comparing with Nontransplantation Models","volume":"15","author":"Arauchi","year":"2009","journal-title":"Tissue Eng Part A"},{"key":"B104","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.addr.2018.04.018","article-title":"Cell encapsulation: Overcoming barriers in cell transplantation in diabetes and beyond","volume":"139","author":"Farina","year":"2019","journal-title":"Adv Drug Deliv Rev"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915872","article-title":"Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson\u2019s Disease","volume":"382","author":"Schweitzer","year":"2020","journal-title":"N Engl J Med"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2019.04.021","article-title":"Evaluation of Transplanted Autologous Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in Exudative Age-Related Macular Degeneration","volume":"3","author":"Takagi","year":"2019","journal-title":"Ophthalmol Retina"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.666565\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T21:43:28Z","timestamp":1618955008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.666565\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,20]]},"references-count":106,"alternative-id":["10.3389\/fendo.2021.666565"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2021.666565","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,20]]},"article-number":"666565"}}