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Stem cell biology

Hematopoietic stem and progenitor cell signaling in the niche

Abstract

Hematopoietic stem and progenitor cells (HSPCs) are responsible for lifelong maintenance of hematopoiesis through self-renewal and differentiation into mature blood cell lineages. Traditional models hold that HSPCs guard homeostatic function and adapt to regenerative demand by integrating cell-autonomous, intrinsic programs with extrinsic cues from the niche. Despite the biologic significance, little is known about the active roles HSPCs partake in reciprocally shaping the function of their microenvironment. Here, we review evidence of signals emerging from HSPCs through secreted autocrine or paracrine factors, including extracellular vesicles, and via direct contact within the niche. We also discuss the functional impact of direct cellular interactions between hematopoietic elements on niche occupancy in the context of leukemic infiltration. The aggregate data support a model whereby HSPCs are active participants in the dynamic adaptation of the stem cell niche unit during development and homeostasis, and under inflammatory stress, malignancy, or transplantation.

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Fig. 1: Autocrine signals provide multiple mechanisms of governing hematopoietic stem and progenitor cell function.
Fig. 2: Hematopoietic stem and progenitor cells actively modulate cells in their bone marrow niche.
Fig. 3: Cell-cell competition drives predominance of the “fittest” hematopoietic cells.
Fig. 4: Extracellular vesicles mediate crosstalk in the bone marrow microenvironment.

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Acknowledgements

We thank Dr. Peter S. Klein for careful review of the paper and editorial contributions. We also acknowledge many colleagues whose relevant research in the field we were not able to cite due to space limitations.

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Correspondence to Peter Kurre.

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Hurwitz, S.N., Jung, S.K. & Kurre, P. Hematopoietic stem and progenitor cell signaling in the niche. Leukemia 34, 3136–3148 (2020). https://doi.org/10.1038/s41375-020-01062-8

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