SLAM Family Receptors Distinguish Hematopoietic Stem and Progenitor Cells and Reveal Endothelial Niches for Stem Cells
Open accessAbstract
To improve our ability to identify hematopoietic stem cells (HSCs) and their localization in vivo, we compared the gene expression profiles of highly purified HSCs and non-self-renewing multipotent hematopoietic progenitors (MPPs). Cell surface receptors of the SLAM family, including CD150, CD244, and CD48, were differentially expressed among functionally distinct progenitors. HSCs were highly purified as CD150(+)CD244(-)CD48(-) cells while MPPs were CD244(+)CD150(-)CD48(-) and most restricted progenitors were CD48(+)CD244(+)CD150(-). The primitiveness of hematopoietic progenitors could thus be predicted based on the combination of SLAM family members they expressed. This is the first family of receptors whose combinatorial expression precisely distinguishes stem and progenitor cells. The ability to purify HSCs based on a simple combination of SLAM receptors allowed us to identify HSCs in tissue sections. Many HSCs were associated with sinusoidal endothelium in spleen and bone marrow, though some HSCs were associated with endosteum. HSCs thus occupy multiple niches, including sinusoidal endothelium in diverse tissues.
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Chronic IL-1β triggers significant expansion of HSC and MPP populations, specifically MPPMkE and MPPGM, in PU.1 +/+ mice.
“Chronic IL-1β also triggered significant expansion of HSC (HSC; Lin−/c-Kit+/Sca-1+/Flk2-/CD48-/CD150+) (Kiel et al., 2005) and MPP populations, specifically the megakaryocyte/erythroid-biased multipotent progenitor (MPPMkE; Lin−/c-Kit+/Sca-1+/Flk2-/CD48+/CD150+; also known as MPP2) and granulocyte/macrophage-biased (MPPGM; Lin−/c-Kit+/Sca-1+/Flk2-/CD48-/CD150-; also known as MPP3) in PU.1 +/+ mice”
From PU.1 is required to restrain myelopoiesis during chronic inflammatory stress (2023) · cites this paper as Kiel et al., 2005
The citation is attached to the HSC marker definition, not the reported IL-1β-induced expansion. In Results (page unavailable), the paper identifies HSCs enriched among CD150+CD48−Sca-1+Lineage−c-kit+ cells, supporting most of that definition. It does not establish the additional Flk2− criterion in the cited marker combination. (LLM, conf=0.86)
Experimental — accuracy not yet measuredBmi1-deficient cells have increased intracellular reactive oxygen species.
“Assessment of unfractionated bone marrow, purified LSK cells and bone marrow cells expressing SLAM family receptors previously shown to allow for enrichment of long-term HSC cells (LT-HSCs)11 demonstrated that the absence of Bmi1–/– resulted in increased levels of ROS (Fig. 1a and Supplementary Fig. 1).”
From Bmi1 regulates mitochondrial function and the DNA damage response pathway (2009) · cites this paper as [11]
In two additional experiments, comets of over two thousand young and old HSCs purified using an alternative HSC marker combination (LKSCD150+CD48−) were assayed.
“In two additional experiments, we assayed comets of over two thousand young and old HSCs purified using an alternative cell surface marker combination for HSCs-LKSCD150+CD48−”
From Quiescent Hematopoietic Stem Cells Accumulate DNA Damage during Aging that Is Repaired upon Entry into Cell Cycle (2014) · cites this paper as Kiel et al., 2005
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- Authors
- Kiel, M. J., Yilmaz, Ö. H., Iwashita, T., Yilmaz, O. H., Terhorst, C., & Morrison, S. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Morrison, Sean J.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 121
- Issue
- 7
- Pages
- 1109-1121
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2077330278
- Cited by
- 3,168
- References
- 74
- Citations by year
- 2026: 35 · 2025: 74 · 2024: 96 · 2023: 101 · 2022: 101 · 2021: 150 · 2020: 134 · 2019: 145 · 2018: 144 · 2017: 157 · 2016: 186 · 2015: 174 · 2014: 196 · 2013: 220 · 2012: 224
- FWCI
- 85.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Army Research Office (DAAD19-03-1-0168)
- National Institutes of Health (R21 HD40760, CA46592)
- University of Michigan
- Howard Hughes Medical Institute
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- SLAM family receptors, hematopoietic stem cells, hematopoietic progenitor cells, CD150, CD244, CD48, sinusoidal endothelium, endosteum, spleen, bone marrow, HSC niche
- MeSH terms
- Signaling Lymphocytic Activation Molecule Family, Signaling Lymphocytic Activation Molecule Family Member 1, CD48 Antigen, Animals, Bone Marrow, Cell Differentiation, Cell Separation, Female, Flow Cytometry, Glycoproteins, Hematopoiesis, Hematopoietic Stem Cells, Immunoglobulins, Male, Membrane Glycoproteins, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred DBA, Receptors, Cell Surface, Receptors, Immunologic, Spleen, Stem Cells, Biomarkers, Antigens, CD, Hematopoietic Stem Cell Transplantation, Cell Lineage, Endothelial Cells, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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