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Cell Stem Cell. 2015 Nov 5;17(5):527-42. doi: 10.1016/j.stem.2015.09.004. Epub 2015 Oct 22.

Regeneration of Thyroid Function by Transplantation of Differentiated Pluripotent Stem Cells.

Author information

1
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA.
2
Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
3
Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
4
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
5
Longwood Small Animal Imaging Facility, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
6
Division of Pulmonary Biology, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
7
Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
8
Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
9
Breathing Institute at the Children's Hospital Colorado and Section of Pediatric Pulmonary Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
10
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. Electronic address: thollenb@bidmc.harvard.edu.
11
Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: dkotton@bu.edu.

Abstract

Differentiation of functional thyroid epithelia from pluripotent stem cells (PSCs) holds the potential for application in regenerative medicine. However, progress toward this goal is hampered by incomplete understanding of the signaling pathways needed for directed differentiation without forced overexpression of exogenous transgenes. Here we use mouse PSCs to identify key conserved roles for BMP and FGF signaling in regulating thyroid lineage specification from foregut endoderm in mouse and Xenopus. Thyroid progenitors derived from mouse PSCs can be matured into thyroid follicular organoids that provide functional secretion of thyroid hormones in vivo and rescue hypothyroid mice after transplantation. Moreover, by stimulating the same pathways, we were also able to derive human thyroid progenitors from normal and disease-specific iPSCs generated from patients with hypothyroidism resulting from NKX2-1 haploinsufficiency. Our studies have therefore uncovered the regulatory mechanisms that underlie early thyroid organogenesis and provide a significant step toward cell-based regenerative therapy for hypothyroidism.

PMID:
26593959
PMCID:
PMC4666682
DOI:
10.1016/j.stem.2015.09.004
[Indexed for MEDLINE]
Free PMC Article

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