SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells

Mark J. Kiel; Ömer H. Yilmaz; Toshihide Iwashita; Osman H. Yilmaz; Cox Terhorst; Sean J. Morrison

doi:10.1016/j.cell.2005.05.026

SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells

Mark J. Kiel, Ömer H. Yilmaz, Toshihide Iwashita, Osman H. Yilmaz, Cox Terhorst, Sean J. Morrison

Research output: Contribution to journal › Article › peer-review

2527 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1109-1121
Number of pages	13
Journal	Cell
Volume	121
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2005.05.026
State	Published - Jul 1 2005

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2005.05.026

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@article{0f2361e02c524e3bbd84259f07350e6c,

title = "SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells",

abstract = "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.",

author = "Kiel, {Mark J.} and Yilmaz, {{\"O}mer H.} and Toshihide Iwashita and Yilmaz, {Osman H.} and Cox Terhorst and Morrison, {Sean J.}",

note = "Funding Information: This work was supported by the Howard Hughes Medical Institute, the National Institutes of Health (R21 HD40760), and the U.S. Army Research Office (DAAD19-03-1-0168). M.J.K. was supported by a Medical Scientist Training Program Fellowship, and O.H.Y. was supported by a predoctoral fellowship from the University of Michigan (UM) Institute of Gerontology. The authors are grateful to Dan Cua at DNAX for providing antibody against CD150. Thanks to David Adams, Anne Marie Deslaurier, Martin White, and the University of Michigan Flow Cytometry Core Facility. Flow cytometry was supported in part by the UM-Comprehensive Cancer, NIH CA46592. Thanks to Elizabeth Smith (Hybridoma Core Facility) for antibody production, supported in part through the Rheumatic Core Disease Center (1 P30 AR48310). Thanks to Dave Misek, Rork Kuick, and Ron Koenig of the Michigan Diabetes Research and Training Center (NIH DK58771) for assistance with microarray analysis and to John Baker for bone sectioning. ",

year = "2005",

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doi = "10.1016/j.cell.2005.05.026",

language = "English (US)",

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T1 - SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells

AU - Kiel, Mark J.

AU - Yilmaz, Ömer H.

AU - Iwashita, Toshihide

AU - Yilmaz, Osman H.

AU - Terhorst, Cox

AU - Morrison, Sean J.

N1 - Funding Information: This work was supported by the Howard Hughes Medical Institute, the National Institutes of Health (R21 HD40760), and the U.S. Army Research Office (DAAD19-03-1-0168). M.J.K. was supported by a Medical Scientist Training Program Fellowship, and O.H.Y. was supported by a predoctoral fellowship from the University of Michigan (UM) Institute of Gerontology. The authors are grateful to Dan Cua at DNAX for providing antibody against CD150. Thanks to David Adams, Anne Marie Deslaurier, Martin White, and the University of Michigan Flow Cytometry Core Facility. Flow cytometry was supported in part by the UM-Comprehensive Cancer, NIH CA46592. Thanks to Elizabeth Smith (Hybridoma Core Facility) for antibody production, supported in part through the Rheumatic Core Disease Center (1 P30 AR48310). Thanks to Dave Misek, Rork Kuick, and Ron Koenig of the Michigan Diabetes Research and Training Center (NIH DK58771) for assistance with microarray analysis and to John Baker for bone sectioning.

PY - 2005/7/1

Y1 - 2005/7/1

N2 - 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.

AB - 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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JO - Cell

JF - Cell

IS - 7

ER -

SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells

Abstract

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