期刊
CELL STEM CELL
卷 10, 期 4, 页码 398-411出版社
CELL PRESS
DOI: 10.1016/j.stem.2012.01.019
关键词
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资金
- NIH [PO1 HL047049-16A1, 1RC2HL101535-01, 1R01 HL095993-01, 1R01 HL108678, T32 HL007035, R01 HL111574]
- USAMRRA
- Alpha-1 Foundation
- ARC from Evans Center for Interdisciplinary Research at Boston University
- ATS/ChILD Foundation
Two populations of Nicx2-1+ progenitors in the developing foregut endoderm give rise to the entire postnatal lung and thyroid epithelium, but little is known about these cells because they are difficult to isolate in a pure form. We demonstrate here the purification and directed differentiation of primordial lung and thyroid progenitors derived from mouse embryonic stem cells (ESCs). Inhibition of TGF beta and BMP signaling, followed by combinatorial stimulation of BMP and FGF signaling, can specify these cells efficiently from definitive endodermal precursors. When derived using Nkx2-1(GFP) knockin reporter ESCs, these progenitors can be purified for expansion in culture and have a transcriptome that overlaps with developing lung epithelium. Upon induction, they can express a broad repertoire of markers indicative of lung and thyroid lineages and can recellularize a 3D lung tissue scaffold. Thus, we have derived a pure population of progenitors able to recapitulate the developmental milestones of lung/thyroid development.
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