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Cited by 384Pluripotent Stem Cells ResearchDevelopmental Biology and Gene RegulationCancer Cells and Metastasis

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

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Longmire, Tyler A., Ikonomou, Laertis, Hawkins, Finn, Christodoulou, Constantina, Cao, Yuxia, Jean, J.C., Kwok, Letty W., Mou, Hongmei +9 more·2012·Cell Stem Cell
DOI 10.1016/j.stem.2012.01.019PMC PMC3322392
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Abstract

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.

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  • Using mouse embryonic stem cells, primordial lung and thyroid progenitors were obtained by manipulating TGFβ, BMP, and FGF signaling pathways.

    “Using mouse embryonic stem cells (ESCs), primordial lung and thyroid progenitors were obtained by manipulating the transforming growth factor β, bone morphogenic protein, and fibroblast growth factor signaling pathways (66).”

    From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [66]

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References 61 · Cited by 384

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Authors
Longmire, T. A., Ikonomou, L., Hawkins, F., Christodoulou, C., Cao, Y., Jean, J. C., Kwok, L. W., Mou, H., Rajagopal, J., Shen, S. S., Dowton, A. A., Serra, M., Weiss, D. J., Green, M. D., Snoeck, H.-W., Ramirez, M. I., & Kotton, D. N.
Affiliations
  • Boston University (US)
  • Massachusetts General Hospital (US)
  • University of Vermont (US)
  • Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Kotton, Darrell N.
ORCID
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2012-04
Volume
10
Issue
4
Pages
398-411
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
DOI
10.1016/j.stem.2012.01.019
PMC
PMC3322392
OpenAlex
W1979927933
Cited by
384
References
61
Citations by year
2026: 11 · 2025: 15 · 2024: 18 · 2023: 27 · 2022: 21 · 2021: 30 · 2020: 29 · 2019: 23 · 2018: 23 · 2017: 37 · 2016: 23 · 2015: 36 · 2014: 46 · 2013: 31 · 2012: 13
FWCI
16.21
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • OpenBU (Boston University) (submittedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (RC2HL101535, R01HL108678, R21HL109786, R21HL108055, P01HL047049, R01HL111574, T32HL007035, R01HL095993)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
TTF-1, embryonic stem cells, foregut endoderm, definitive endoderm, TGF-beta inhibition, BMP signaling, FGF signaling, lineage specification, lung development, thyroid development
MeSH terms
Animals, Cell Separation, Fibroblast Growth Factors, Lung, Mice, Transgenic, Thyroid Gland, Signal Transduction, Bone Morphogenetic Proteins, Mice, Embryonic Stem Cells, Tissue Scaffolds

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