Journal
TRENDS IN IMMUNOLOGY
Volume 40, Issue 11, Pages 1053-1070Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.it.2019.09.006
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Funding
- Canadian Institutes of Health Research
- Canadian Cancer Society Research Institute
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Hematopoietic stem cells (HSCs) self-renew or differentiate into blood cell lineages following extrinsic cues propagated in specialized niches. Support cells and soluble factors in the niche respond to stress and enable progenitor activity. Metalloproteases (MMPs, ADAMs, ADAMTSs' and their inhibitors (TIMPs) control certain physical and biochemical features of the niche by altering protease-dependent bioavailability of local niche factors (e.g., CXCL12, SCF, TGF beta, VEGF), matrix turnover, and cellular interactions. With over 40 examples of diverse metallopro tease substrates known to trigger fate-changing decisions, the spatially confined activity of this multi-member protease family is ideally positioned to constitute a higher order control over hematopoiesis. Comprehension of regulated proteolysis in the bone marrow may fuel innovative strategies to harness HSC fate and function.
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