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

• DOI: 10.1016/j.stemcr.2016.12.024
• Publication Date: 2017-02-03T06:00:25Z
• Authors: 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. Hollen...; Pankaj Mehta; Darrell N. Kotton; Laertis Ikonomou
• Keywords: Matrigel

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