Journal
CELL
Volume 160, Issue 1-2, Pages 269-284Publisher
CELL PRESS
DOI: 10.1016/j.cell.2014.11.042
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Funding
- NIH [NIH 5U54 CA126513, R01 RHL115145A, NIH AR056246, EB006834]
- American Cancer Society
- NH&MRC and Menzies Foundation
- Cancer Council SA's Beat Cancer
- State Government of South Australia through the Department of Health, Gastroenterological Society of Australia
- American Gastroenterological Association
- American Association for Cancer Research
- Royal Australasian College of Physicians
- Ines Mandl Postdoctoral research fellowship Columbia University
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The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fate-mapping experiments. We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow. OCR stem cells self-renew and generate osteoblasts, chondrocytes, and reticular marrow stromal cells, but not adipocytes. OCR stem cells are concentrated within the metaphysis of long bones not in the perisinusoidal space and are needed for bone development, bone remodeling, and fracture repair. Grem1 expression also identifies intestinal reticular stem cells (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal sheath. Grem1 expression identifies distinct connective tissue stem cells in both the bone (OCR stem cells) and the intestine (iRSCs).
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