Mechanoregulation in Hematopoiesis and Hematologic Disorders
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CLASSICAL SIGNALLING PATHWAYS (A CARDOSO & A CARLESSO, SECTION EDITORS)
Mechanoregulation in Hematopoiesis and Hematologic Disorders Paulina D. Horton 1,2 & Sandeep Dumbali 1,2 & Pamela L. Wenzel 1,2
# The Author(s) 2020
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 . Hematopoietic stem cells . Hematopoiesis . Hematological disorders . Mechanobiology . Mechanosensors
Introduction Hematopoietic stem cells (HSCs) are a rare population of cells capable of self-renewal that are responsible for establishment and maintenance of the blood system [1]. Due to the relatively short lifespan of many mature types of blood cells, HSCs are necessary to replenish these cells throughout
Paulina D. Horton and Sandeep Dumbali contributed equally to this work. This article is part of the Topical Collection on Classical Signalling Pathways * Pamela L. Wenzel [email protected] 1
Department of Integrative Biology & Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
2
Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
the lifetime of the individual in a process termed hematopoiesis [2]. Their capacity to self-renew and differentiate into multiple blood lineages long-term separates HSCs from committed progenitor cells, whose differentiative potential is generally restricted to a few or a single lineage and usually exhausts after a few weeks [3]. It is because of the HSC’s self-renewal capability that HSC transplantation, the standard of care for most hematologic malignancies and bone marrow failure syndromes, is possible [4]. Yet, clinical success following HSC transplan
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