Thyroid Progenitors Are Robustly Derived from Embryonic Stem Cells through Transient, Developmental Stage-Specific Overexpression of Nkx2-1

Keri Dame; Steven Cincotta; Alex H. Lang; Reeti M. Sanghrajka; Liye Zhang; Jinyoung Choi; Letty Kwok; Talitha Wilson; Maciej M. Kańduła; Stefano Monti; Anthony N. Hollenberg; Pankaj Mehta; Darrell N. Kotton; Laertis Ikonomou

doi:10.1016/j.stemcr.2016.12.024

Stem Cell Reports (Feb 2017)

Thyroid Progenitors Are Robustly Derived from Embryonic Stem Cells through Transient, Developmental Stage-Specific Overexpression of Nkx2-1

Keri Dame,
Steven Cincotta,
Alex H. Lang,
Reeti M. Sanghrajka,
Liye Zhang,
Jinyoung Choi,
Letty Kwok,
Talitha Wilson,
Maciej M. Kańduła,
Stefano Monti,
Anthony N. Hollenberg,
Pankaj Mehta,
Darrell N. Kotton,
Laertis Ikonomou

Affiliations

Keri Dame: Center for Regenerative Medicine, Boston Medical Center and Boston University, 670 Albany Street, 2nd Floor CReM, Boston, MA 02118, USA
Steven Cincotta: Center for Regenerative Medicine, Boston Medical Center and Boston University, 670 Albany Street, 2nd Floor CReM, Boston, MA 02118, USA
Alex H. Lang: Department of Physics, Boston University, Boston, MA 02215, USA
Reeti M. Sanghrajka: Center for Regenerative Medicine, Boston Medical Center and Boston University, 670 Albany Street, 2nd Floor CReM, Boston, MA 02118, USA
Liye Zhang: Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118, USA
Jinyoung Choi: Center for Regenerative Medicine, Boston Medical Center and Boston University, 670 Albany Street, 2nd Floor CReM, Boston, MA 02118, USA
Letty Kwok: The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
Talitha Wilson: The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
Maciej M. Kańduła: Chair of Bioinformatics Research Group, Boku University, 1190 Vienna, Austria
Stefano Monti: Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118, USA
Anthony N. Hollenberg: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Pankaj Mehta: Department of Physics, Boston University, Boston, MA 02215, USA
Darrell N. Kotton: Center for Regenerative Medicine, Boston Medical Center and Boston University, 670 Albany Street, 2nd Floor CReM, Boston, MA 02118, USA
Laertis Ikonomou: Center for Regenerative Medicine, Boston Medical Center and Boston University, 670 Albany Street, 2nd Floor CReM, Boston, MA 02118, USA

DOI: https://doi.org/10.1016/j.stemcr.2016.12.024
Journal volume & issue: Vol. 8, no. 2
pp. 216 – 225

Abstract

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The clinical importance of anterior foregut endoderm (AFE) derivatives, such as thyrocytes, has led to intense research efforts for their derivation through directed differentiation of pluripotent stem cells (PSCs). Here, we identify transient overexpression of the transcription factor (TF) NKX2-1 as a powerful inductive signal for the robust derivation of thyrocyte-like cells from mouse PSC-derived AFE. This effect is highly developmental stage specific and dependent on FOXA2 expression levels and precise modulation of BMP and FGF signaling. The majority of the resulting cells express thyroid TFs (Nkx2-1, Pax8, Foxe1, Hhex) and thyroid hormone synthesis-related genes (Tg, Tpo, Nis, Iyd) at levels similar to adult mouse thyroid and give rise to functional follicle-like epithelial structures in Matrigel culture. Our findings demonstrate that NKX2-1 overexpression converts AFE to thyroid epithelium in a developmental time-sensitive manner and suggest a general methodology for manipulation of cell-fate decisions of developmental intermediates.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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