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Free keywords:
COLONY-STIMULATING FACTOR; BONE-MARROW MICROENVIRONMENT; CHRONIC
MYELOGENOUS LEUKEMIA; MURINE YOLK-SAC; PLACENTAL EXTRACELLULAR-MATRIX;
LATE ACTIVATION ANTIGEN-4; FOCAL ADHESION PROTEINS; LONG-TERM; FETAL
LIVER; IN-VIVOCell Biology; Developmental Biology;
Abstract:
Hematopoietic stem cells (HSCs), the apex of the hierarchically organized blood cell production system, are generated in the yolk sac, aorta-gonad-mesonephros region and placenta of the developing embryo. To maintain life-long hematopoiesis, HSCs emigrate from their site of origin and seed in distinct microenvironments, called niches, of fetal liver and bone marrow where they receive supportive signals for self-renewal, expansion and production of hematopoietic progenitor cells (HPCs), which in turn orchestrate the production of the hematopoietic effector cells. The interactions of hematopoietic stem and progenitor cells (HSPCs) with niche components are to a large part mediated by the integrin superfamily of adhesion molecules. Here, we summarize the current knowledge regarding the functional properties of integrins and their activators, Talin-1 and Kindlin-3, for HSPC generation, function and fate decisions during development and in adulthood. In addition, we discuss integrin-mediated mechanosensing for HSC-niche interactions, ex vivo protocols aimed at expanding HSCs for therapeutic use, and recent approaches targeting the integrin-mediated adhesion in leukemia-inducing HSCs in their protecting, malignant niches.
