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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kurmann, AA; Serra, M; Hawkins, F; Rankin, SA; Mori, M; Astapova, I; Ullas, S; Lin, S; Bilodeau, M; Rossant, J; Jean, JC; Ikonomou, L; Deterding, RR; Shannon, JM; Zorn, AM; Hollenberg, AN; Kotton, DN

Published Date

  • November 5, 2015

Published In

Volume / Issue

  • 17 / 5

Start / End Page

  • 527 - 542

PubMed ID

  • 26593959

Pubmed Central ID

  • 26593959

Electronic International Standard Serial Number (EISSN)

  • 1875-9777

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2015.09.004

Language

  • eng

Conference Location

  • United States