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

被引：35

作者：

Dame, Keri ^{[1
,2
,3
]}

Cincotta, Steven ^{[1
,2
,3
]}

Lang, Alex H. ^{[4
]}

Sanghrajka, Reeti M. ^{[1
,2
,3
]}

Zhang, Liye ^{[5
]}

Choi, Jinyoung ^{[1
,2
,6
]}

Kwok, Letty ^{[3
]}

Wilson, Talitha ^{[3
]}

Kandula, Maciej M. ^{[7
]}

Monti, Stefano

Hollenberg, Anthony N. ^{[6
]}

Mehta, Pankaj ^{[4
]}

Kotton, Darrell N. ^{[1
,2
,3
]}

Ikonomou, Laertis ^{[1
,2
,3
]}

机构：

[1] Boston Med Ctr, Ctr Regenerat Med, 670 Albany St,2nd Floor CReM, Boston, MA 02118 USA

[2] Boston Univ, 670 Albany St,2nd Floor CReM, Boston, MA 02118 USA

[3] Boston Univ, Dept Med, Ctr Pulm, Sch Med, Boston, MA 02118 USA

[4] Boston Univ, Dept Phys, Boston, MA 02215 USA

[5] Boston Univ, Sect Computat Biomed, Sch Med, Boston, MA 02118 USA

[6] Harvard Med Sch, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[7] Boku Univ, Chair Bioinformat Res Grp, A-1190 Vienna, Austria

来源：

STEM CELL REPORTS | 2017年 / 8卷 / 02期

关键词：

ENHANCER-BINDING PROTEIN; MOUSE; LUNG; EXPRESSION; ENDODERM; GENERATION; DERIVATION; GENE; ORGANOGENESIS; INDUCTION;

D O I：

10.1016/j.stemcr.2016.12.024

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：216 / 225

页数：10

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