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Metalloproteases: On the Watch in the Hematopoietic Niche

Sanjay Saw1, Ashley Weiss2, Rama Khokha2

  • 1Princess Margaret Cancer Centre, University Health Network, Department of Medical Biophysics, University of Toronto, Toronto, Canada.

Trends in Immunology
|October 25, 2019
PubMed

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, TGFβ, VEGF), matrix turnover, and cellular interactions. With over 40 examples of diverse metalloprotease 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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