Portal de Periódicos da CAPES

Efficient Derivation of Purified Lung and Thyroid Progenitors from Embryonic Stem Cells

2012; Elsevier BV; Volume: 10; Issue: 4 Linguagem: Inglês

10.1016/j.stem.2012.01.019

1934-5909

Tyler A. Longmire, Laertis Ikonomou, Finn Hawkins, Constantina Christodoulou, Yuxia Cao, J.C. Jean, Letty W. Kwok, Hongmei Mou, Jayaraj Rajagopal, Steven S. Shen, Anne A. Dowton, Maria Paola Serra, Daniel J. Weiss, Michael D. Green, Hans-Willem Snoeck, María I. Ramirez, Darrell N. Kotton,

Congenital heart defects research

Two populations of Nkx2-1+ 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 TGFβ and BMP signaling, followed by combinatorial stimulation of BMP and FGF signaling, can specify these cells efficiently from definitive endodermal precursors. When derived using Nkx2-1GFP 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.