Editors' ChoiceStem Cells

Who Is in the House?

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Science Translational Medicine  29 Feb 2012:
Vol. 4, Issue 123, pp. 123ec37
DOI: 10.1126/scitranslmed.3003901

Hematopoietic stem cells (HSCs) are the driving force of the blood: Just one transferred HSC can reconstitute all blood cells in the recipient. These long-lived cells can be quiescent over long periods of time but may suddenly burst into activity, replenishing the shorter-lived circulating cells that take care of oxygen supply, immune defense, healing, and clotting. Hence, HSCs have been in the limelight for decades, but their scant numbers imposed difficulties on unraveling their secrets—especially their propensity to proliferate, differentiate, and migrate.

HSCs live in niches in the bone marrow—areas critical for either maintaining HSC quiescence or inducing differentiation into more specialized blood cells. A handful of cell types play a role in HSC “housekeeping” in these niches: Endothelial cells, osteoblasts, perivascular cells, nestin+ cells, mesenchymal stem cells, fibroblasts, and macrophages may secrete retention factors and provide a microenvironment to regulate HSC activity. Now, Ding et al. provide new answers on HSC housekeeping by coexpressing stem cell factor (SCF) with green fluorescent protein. After identifying green endothelial and perivascular cells surrounding bone marrow sinusoids in Scfgfp/+mice, they knocked out Scf in these specific cells as well as in some other of the usual suspects listed above using a floxed allele of Scf. When Scf was conditionally deleted in either endothelial or perivascular stromal cells, HSCs left their house in droves. This was not the case when Scf was deleted from osteoblasts or nestin+ cells, which have previously been described as niche candidate cells.

Ding et al. concede that SCF may not be the only factor of importance in niche maintenance and that things may change with increased demands for progeny cells because of disease. However, their work elegantly uses transgenic models to clarify the role of specific cell types in the HSC bone marrow niche. SCF is not the new kid on the block, but enjoys VIP status with HSCs, and by knowing its primary cellular sources during steady state, we may be able to better affect HSC function in health and disease.

L. Ding et al., Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481, 457–62 (2012). [Nature]

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