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Systemic and local regulation of hematopoietic homeostasis in health and disease

Abstract

Hematopoietic stem cells (HSCs) generate all blood cell lineages responsible for tissue oxygenation, life-long hematopoietic homeostasis and immune protection. In adulthood, HSCs primarily reside in the bone marrow (BM) microenvironment, consisting of diverse cell types that constitute the stem cell ‘niche’. The adaptability of the hematopoietic system is required to respond to the needs of the host, whether to maintain normal physiology or during periods of physical, psychosocial or environmental stress. Hematopoietic homeostasis is achieved by intricate coordination of systemic and local factors that orchestrate the function of HSCs throughout life. However, homeostasis is not a static process; it modulates HSC and progenitor activity in response to circadian rhythms coordinated by the central and peripheral nervous systems, inflammatory cues, metabolites and pathologic conditions. Here, we review local and systemic factors that impact hematopoiesis, focusing on the implications of aging, stress and cardiovascular disease.

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Fig. 1: Cellular and molecular organization of the HSC niche.
Fig. 2: Communication between the CNS and the BM.
Fig. 3: CNS-derived signals mediate hematopoiesis and HSC responses to stress, aging and CVD.
Fig. 4: Remodeling the BM microenvironment during aging and CVD.
Fig. 5: Local and systemic factors influencing hematopoiesis and HSC function.

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Acknowledgements

M.M. is supported by the American Society of Hematology (ASH) Scholar Award (2023). R.S.C. was supported by NIH T32 HL144456 (NHLBI), NIH F32 HL158084 (NHLBI), the Gottesman Stem Cell Institute Paul S. Frenette Scholars Award and is currently supported by the Cancer Research Institute (CRI) Irvington Postdoctoral Fellowship (CRI4994).

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Carpenter, R.S., Maryanovich, M. Systemic and local regulation of hematopoietic homeostasis in health and disease. Nat Cardiovasc Res 3, 651–665 (2024). https://doi.org/10.1038/s44161-024-00482-4

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