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Nat Methods. 2017 Dec;14(12):1205-1212. doi: 10.1038/nmeth.4498. Epub 2017 Nov 6.

Isolation and 3D expansion of multipotent Sox9+ mouse lung progenitors.

Author information

1
Stem Cell & Regenerative Biology Group, Genome Institute of Singapore, A*STAR, Singapore.
2
Cancer Therapeutics & Stratified Oncology Group, Genome Institute of Singapore, A*STAR, Singapore.
3
The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
4
Department of Biology, Clarkson University, Potsdam, New York, USA.
5
Stanford Institute for Stem Cell Biology and Regenerative Medicine and the Stanford-UC Berkeley Siebel Stem Cell Institute, Stanford University School of Medicine, Stanford, California, USA.

Abstract

Multiple adult tissues are maintained by stem cells of restricted developmental potential which can only form a subset of lineages within the tissue. For instance, the two adult lung epithelial compartments (airways and alveoli) are separately maintained by distinct lineage-restricted stem cells. A challenge has been to obtain multipotent stem cells and/or progenitors that can generate all epithelial cell types of a given tissue. Here we show that mouse Sox9+ multipotent embryonic lung progenitors can be isolated and expanded long term in 3D culture. Cultured Sox9+ progenitors transcriptionally resemble their in vivo counterparts and generate both airway and alveolar cell types in vitro. Sox9+ progenitors that were transplanted into injured adult mouse lungs differentiated into all major airway and alveolar lineages in vivo in a region-appropriate fashion. We propose that a single expandable embryonic lung progenitor population with broader developmental competence may eventually be used as an alternative for region-restricted adult tissue stem cells in regenerative medicine.

PMID:
29106405
DOI:
10.1038/nmeth.4498
[Indexed for MEDLINE]

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