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Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells.

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 Nkx2-1(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.

Pubmed ID: 22482505

Authors

  • Longmire TA
  • Ikonomou L
  • Hawkins F
  • Christodoulou C
  • Cao Y
  • Jean JC
  • Kwok LW
  • Mou H
  • Rajagopal J
  • Shen SS
  • Dowton AA
  • Serra M
  • Weiss DJ
  • Green MD
  • Snoeck HW
  • Ramirez MI
  • Kotton DN

Journal

Cell stem cell

Publication Data

April 6, 2012

Associated Grants

  • Agency: NHLBI NIH HHS, Id: 1R01 HL095993-01
  • Agency: NHLBI NIH HHS, Id: 1R01 HL108678
  • Agency: NHLBI NIH HHS, Id: 1RC2HL101535-01
  • Agency: NHLBI NIH HHS, Id: P01HL047049-16A1
  • Agency: NHLBI NIH HHS, Id: R01 HL095993-01A1
  • Agency: NHLBI NIH HHS, Id: R01 HL108678-01
  • Agency: NHLBI NIH HHS, Id: R01 HL111574
  • Agency: NHLBI NIH HHS, Id: R01 HL111574
  • Agency: NHLBI NIH HHS, Id: R21 HL108055
  • Agency: NHLBI NIH HHS, Id: R21 HL109786
  • Agency: NHLBI NIH HHS, Id: RC2 HL101535-01
  • Agency: NHLBI NIH HHS, Id: T32 HL007035

Mesh Terms

  • Animals
  • Bone Morphogenetic Proteins
  • Cell Separation
  • Embryonic Stem Cells
  • Fibroblast Growth Factors
  • Lung
  • Mice
  • Mice, Transgenic
  • Signal Transduction
  • Thyroid Gland
  • Tissue Scaffolds