Journal
SCIENCE
Volume 333, Issue 6039, Pages 218-221Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1201219
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Funding
- Canadian Institutes for Health Research (CIHR)
- Swiss National Science Foundation
- Roche
- Canadian Cancer Society
- Terry Fox Foundation
- Genome Canada through the Ontario Genomics Institute
- Ontario Institute for Cancer Research with province of Ontario
- Ontario Ministry of Health and Long Term Care (OMOHLTC)
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Lifelong blood cell production is dependent on rare hematopoietic stem cells (HSCs) to perpetually replenish mature cells via a series of lineage-restricted intermediates. Investigating the molecular state of HSCs is contingent on the ability to purify HSCs away from transiently engrafting cells. We demonstrated that human HSCs remain infrequent, using current purification strategies based on Thy1 (CD90) expression. By tracking the expression of several adhesion molecules in HSC-enriched subsets, we revealed CD49f as a specific HSC marker. Single CD49f(+) cells were highly efficient in generating long-term multilineage grafts, and the loss of CD49f expression identified transiently engrafting multipotent progenitors (MPPs). The demarcation of human HSCs and MPPs will enable the investigation of the molecular determinants of HSCs, with a goal of developing stem cell-based therapeutics.
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