Abstract
Purpose of Review
Hematopoietic stem and progenitor cells (HSC/HSPCs) originate in bone marrow (BM) niches and facilitate immune cell production throughout life. Critical signals from physical and soluble factors in the niche, including the native low oxygen (“hypoxic”) environment, regulate the phenotype, function, and cell fate decisions of HSCs. In this review, we highlight foundational knowledge, recent insights detailing the implications of varied oxygen levels in the BM niche and how manipulation of the oxygen environment in experimental conditions impact the data/interpretation of HSC/HSPC populations.
Recent Findings
Using novel techniques, characterization of oxygen tension in distinct BM niches has shaped foundational studies of HSC/HSPC localization and biology. Additional studies utilizing sorted, live HSCs that remain in their physiologic low oxygen environment, rather than exposing them to air and placing them back into low oxygen conditions, continue to advance our knowledge of endogenous HSC phenotype, heterogeneity, signaling, and function/fate decisions.
Summary
The low oxygen (O2) environment of the BM niche plays a vital role in normal and malignant hematopoiesis including HSC/HSPC metabolism, signaling/regulatory mechanisms, quiescence, stem cell fate/differentiation, engraftment/transplantation ability, and therapeutic response. Technological innovations have advanced our current understanding of HSC localization and regulation within the BM niche with respect to the low O2 environment. Initial studies identified unique oxygen gradients as well as loss of HSC after removal from low O2 (i.e., exposure to room air using whole BM). Recent studies being performed with sorted, live HSC/HSPC populations remaining in their native low O2 environment have provided novel insight, direct comparisons, and identification of unique HSC/HSPC subpopulations demonstrating alterations in signaling, heterogeneity, cell fidelity, and enhancement in the HSC/HSPC phenotype/function not identified in previous studies. Further studies of hematopoietic cell subpopulations in their native low O2 environment will shed additional light on endogenous HSC/HSPC biology leading to translational implications for transplantation and therapeutic intervention.
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Paige Dausinas Ni, Chris Basile, Chase Junge, Melissa Hartman, and Heather O’Leary declare that they have no conflict of interest.
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Dausinas Ni, P., Basile, C., Junge, C. et al. Hypoxia and Hematopoiesis. Curr Stem Cell Rep 8, 24–34 (2022). https://doi.org/10.1007/s40778-021-00203-8
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DOI: https://doi.org/10.1007/s40778-021-00203-8