SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors

Hideyuki Oguro, Lei Ding, Sean J. Morrison

Research output: Contribution to journalArticle

238 Citations (Scopus)

Abstract

SUMMARY Hematopoietic stem cells (HSCs) and multipotent hematopoietic progenitors (MPPs) are routinely isolated using various markers but remain heterogeneous. Here we show that four SLAM family markers, CD150, CD48, CD229, and CD244, can distinguish HSCs and MPPs from restricted progenitors and subdivide them into a hierarchy of functionally distinct subpopulations with stepwise changes in cell-cycle status, self-renewal, and reconstituting potential. CD229 expression largely distinguished lymphoid-biased HSCs from rarely dividing myeloid-biased HSCs, enabling prospective enrichment of these HSC subsets. Differences in CD229 and CD244 expression resolved CD150-CD48-/low Lineage-/lowSca-1+c-Kit+ cells into a hierarchy of highly purified MPPs that retained erythroid and platelet potential but exhibited progressive changes in mitotic activity and reconstituting potential. Use of these markers, and reconstitution assays, showed that conditional deletion of Scf from endothelial cells and perivascular stromal cells eliminated the vast majority of bone marrow HSCs, including nearly all CD229-/low HSCs, demonstrating that quiescent HSCs are maintained by a perivascular niche. 2013

Original languageEnglish (US)
Pages (from-to)102-116
Number of pages15
JournalCell Stem Cell
Volume13
Issue number1
DOIs
StatePublished - Jul 3 2013

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Hematopoietic Stem Cells
Stromal Cells
Cell Cycle
Blood Platelets
Endothelial Cells
Bone Marrow

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics
  • Medicine(all)

Cite this

SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors. / Oguro, Hideyuki; Ding, Lei; Morrison, Sean J.

In: Cell Stem Cell, Vol. 13, No. 1, 03.07.2013, p. 102-116.

Research output: Contribution to journalArticle

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N2 - SUMMARY Hematopoietic stem cells (HSCs) and multipotent hematopoietic progenitors (MPPs) are routinely isolated using various markers but remain heterogeneous. Here we show that four SLAM family markers, CD150, CD48, CD229, and CD244, can distinguish HSCs and MPPs from restricted progenitors and subdivide them into a hierarchy of functionally distinct subpopulations with stepwise changes in cell-cycle status, self-renewal, and reconstituting potential. CD229 expression largely distinguished lymphoid-biased HSCs from rarely dividing myeloid-biased HSCs, enabling prospective enrichment of these HSC subsets. Differences in CD229 and CD244 expression resolved CD150-CD48-/low Lineage-/lowSca-1+c-Kit+ cells into a hierarchy of highly purified MPPs that retained erythroid and platelet potential but exhibited progressive changes in mitotic activity and reconstituting potential. Use of these markers, and reconstitution assays, showed that conditional deletion of Scf from endothelial cells and perivascular stromal cells eliminated the vast majority of bone marrow HSCs, including nearly all CD229-/low HSCs, demonstrating that quiescent HSCs are maintained by a perivascular niche. 2013

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