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Cellular Complexity of the Bone Marrow Hematopoietic Stem Cell Niche

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Abstract

The skeleton serves as the principal site for hematopoiesis in adult terrestrial vertebrates. The function of the hematopoietic system is to maintain homeostatic levels of all circulating blood cells, including myeloid cells, lymphoid cells, red blood cells, and platelets. This action requires the daily production of more than 500 billion blood cells. The vast majority of these cells are synthesized in the bone marrow, where they arise from a limited number of hematopoietic stem cells (HSCs) that are multipotent and capable of extensive self-renewal. These attributes of HSCs are best demonstrated by marrow transplantation, where even a single HSC can repopulate the entire hematopoietic system. HSCs are therefore adult stem cells capable of multilineage repopulation, poised between cell fate choices which include quiescence, self-renewal, differentiation, and apoptosis. While HSC fate choices are in part determined by multiple stochastic fluctuations of cell autonomous processes, according to the niche hypothesis, signals from the microenvironment are also likely to determine stem cell fate. While it had long been postulated that signals within the bone marrow could provide regulation of hematopoietic cells, it is only in the past decade that advances in flow cytometry and genetic models have allowed for a deeper understanding of the microenvironmental regulation of HSCs. In this review, we will highlight the cellular regulatory components of the HSC niche.

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Acknowledgements

The authors thank Dr. B. J. Frisch for review of the manuscript and members of the Calvi and Link laboratories for helpful discussions. This work is supported by the National Institutes of Health (NIDDK grants DK076876 and DK081843 to L. M. C. and HL60772 to D. C. L.).

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  1. Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA

    Laura M. Calvi

  2. Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Daniel C. Link

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  1. Laura M. Calvi
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  2. Daniel C. Link
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Correspondence to Laura M. Calvi.

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The authors have stated that they have no conflict of interest.

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Calvi, L.M., Link, D.C. Cellular Complexity of the Bone Marrow Hematopoietic Stem Cell Niche. Calcif Tissue Int 94, 112–124 (2014). https://doi.org/10.1007/s00223-013-9805-8

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  • DOI: https://doi.org/10.1007/s00223-013-9805-8

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