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. 2020 Sep;6(3):86-95.
doi: 10.1007/s40778-020-00172-4. Epub 2020 May 21.

Mechanoregulation in hematopoiesis and hematologic disorders

Paulina D Horton  1   2 , Sandeep Dumbali  1   2 , Pamela L Wenzel  1   2
Affiliations

Mechanoregulation in hematopoiesis and hematologic disorders

Paulina D Horton et al. Curr Stem Cell Rep. 2020 Sep.

Abstract

Purpose of review: Hematopoietic stem cells (HSCs) are reliant on intrinsic and extrinsic factors for tight control of self-renewal, quiescence, differentiation, and homing. Given the intimate relationship between HSCs and their niche, increasing numbers of studies are examining how biophysical cues in the hematopoietic microenvironment impact HSC functions.

Recent findings: Numerous mechanosensors are present on hematopoietic cells, including integrins, mechanosensitive ion channels, and primary cilia. Integrin-ligand adhesion, in particular, has been found to be critical for homing and anchoring of HSCs and progenitors in the bone marrow. Integrin-mediated interactions with ligands present on extracellular matrix and endothelial cells are key to establishing long-term engraftment and quiescence of HSCs. Importantly, disruption in the architecture and cellular composition of the bone marrow associated with conditioning regimens and primary myelofibrosis exposes HSCs to a profoundly distinct mechanical environment, with potential implications for progression of hematologic dysfunction and pathologies.

Summary: Study of the mechanobiological signals that govern hematopoiesis represents an important future step toward understanding HSC biology in homeostasis, aging, and cancer.

Keywords: Biomechanical force; hematological disorders; hematopoiesis; hematopoietic stem cells; mechanobiology; mechanosensors.

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Conflict of interest statement

Compliance with Ethical Standards Conflict of Interest All authors declare that they have no conflicts of interest.

Figures

Figure 1.
Figure 1.. Bone marrow architecture and mechanoregulation.
A. The bone marrow is comprised of a complex milieu of cells interlaced with blood vessels and nerves, working in concert to support hematopoiesis. An emerging concept in the field is that the marrow houses distinct hematopoietic niches for subpopulations of HSCs with functional heterogeneity. B. Integrins, mechanosensitive ion channels, and primary cilia sense mechanical features of the hematopoietic niche. Activation of mechanotransduction pathways alter gene expression and cell behavior critical for homeostasis and response to stress.
See this image and copyright information in PMC

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