Journal
STEM CELLS
Volume 31, Issue 12, Pages 2759-2766Publisher
WILEY-BLACKWELL
DOI: 10.1002/stem.1413
Keywords
Adult stem cells; Bone marrow; Differentiation; Tissue regeneration; Fluorescent protein reporter genes; Plasticity; Respiratory tract; Stem cell transplantation
Categories
Funding
- Yale Center of Excellence in Molecular Hematology [DK072442]
- Yale Cancer Center [CA16359]
- Basil O'Conner March of Dimes Starter Award
- Harvard Stem Cell Institute
- [HL073742]
- [DK61846]
- [1U01HL099997-01]
- [RO1 HL090136]
- [U01 HL100402]
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The view that adult stem cells are lineage restricted has been challenged by numerous reports of bone marrow (BM)-derived cells giving rise to epithelial cells. Previously, we demonstrated that nonhematopoietic BM cells are the primary source of BM-derived lung epithelial cells. Here, we tested the hypothesis that very small embryonic like cells (VSELs) are responsible for this engraftment. We directly compared the level of BM-derived epithelial cells after transplantation of VSELs, hematopoietic stem/progenitor cells, or other nonhematopoietic cells. VSELs clearly had the highest rate of forming epithelial cells in the lung. By transplanting VSELs from donor mice expressing H2B-GFP under a type 2 pneumocyte-specific promoter, we demonstrate that this engraftment occurs by differentiation and not fusion. This is the first report of VSELs differentiating into an endodermal lineage in vivo, thereby potentially crossing germ layer lineages. Our data suggest that Oct4+ VSELs in the adult BM exhibit broad differentiation potential.
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