دورية أكاديمية
Thyroid Progenitors Are Robustly Derived from Embryonic Stem Cells through Transient, Developmental Stage-Specific Overexpression of Nkx2-1
العنوان: | Thyroid Progenitors Are Robustly Derived from Embryonic Stem Cells through Transient, Developmental Stage-Specific Overexpression of Nkx2-1 |
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المؤلفون: | 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 |
المصدر: | Stem Cell Reports, Vol 8, Iss 2, Pp 216-225 (2017) |
بيانات النشر: | Elsevier, 2017. |
سنة النشر: | 2017 |
المجموعة: | LCC:Medicine (General) LCC:Biology (General) |
مصطلحات موضوعية: | mouse embryonic stem cell, pluripotent stem cell, directed differentiation, thyroid development, Nkx2-1, transcription factor, overexpression, progenitor specification, foregut, inducible, Medicine (General), R5-920, Biology (General), QH301-705.5 |
الوصف: | 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. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2213-6711 |
Relation: | http://www.sciencedirect.com/science/article/pii/S2213671116303149; https://doaj.org/toc/2213-6711 |
DOI: | 10.1016/j.stemcr.2016.12.024 |
URL الوصول: | https://doaj.org/article/8ebe20c6946e4cd081868ef327d1beec |
رقم الأكسشن: | edsdoj.8ebe20c6946e4cd081868ef327d1beec |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 22136711 |
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DOI: | 10.1016/j.stemcr.2016.12.024 |