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Flk-2 is a marker in hematopoietic stem cell differentiation: A simple method to isolate long-term stem cells
Open accessAbstract
Clonogenic multipotent mouse hematopoietic stem cells (HSCs) and progenitor cells are contained within the c-kit + (K) lineage −/lo (L) Sca-1 + (S) population of hematopoietic cells; long-term (LT) and short-term (ST) HSCs are Thy-1.1 lo . c-kit is a member of the receptor tyrosine kinase family, a class of receptors that are important in the proliferation and differentiation of hematopoietic cells. To establish whether the Flk-2/Flt3 receptor tyrosine kinase was expressed on the most primitive LT-HSCs, we sorted highly purified multipotent stem and progenitor cells on the basis of Flk-2 surface expression and used them in competitive reconstitution assays. Low numbers of Flk-2 − HSCs gave rise to long-term multilineage reconstitution in the majority of recipients, whereas the transfer of Flk-2 + multipotent cells resulted in mostly short-term multilineage reconstitution. The KLS subset of adult mouse bone marrow was analyzed for Flk-2 and Thy-1.1 expression. Three phenotypically and functionally distinct populations were isolated: Thy lo Flk-2 − (LT-HSCs), Thy lo Flk-2 + (ST-HSCs), and Thy − Flk-2 + multipotent progenitors. The loss of Thy-1.1 and gain of Flk-2 expression marks the loss of self-renewal in HSC maturation. The addition of Flk-2 antibody to the lineage mix allows direct isolation of LT-HSC from adult bone marrow as c-kit + lin − Sca-1 + Flk-2 − from many strains of mice. Fetal liver HSCs are contained within Flk-2 − and Flk-2 + KTLS cells.
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Metadata
- Authors
- Christensen, J. L., & Weissman, I. L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-11-27
- Volume
- 98
- Issue
- 25
- Pages
- 14541-14546
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2100378064
- Cited by
- 785
- References
- 2
- FWCI
- 12.20
- Type
- journal article
- Language
- en
- Open access
- green
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