Membrane-bound SCF and VCAM-1 synergistically regulate the morphology of hematopoietic stem cells

  • J Cell Biol. 2021 Oct 4;220(10):e202010118. doi: 10.1083/jcb.202010118.
Jia Hao  1 ,  Hao Zhou  1 ,  Kristen Nemes  1 ,  Daniel Yen  1 ,  Winfield Zhao  1 ,  Charles Bramlett  2 ,  Bowen Wang  2 ,  Rong Lu  1  2  3  4 ,  Keyue Shen  1  3  5
Affiliations
  • 1. Department of Biomedical Engineering, University of Southern California, Los Angeles, CA.
  • 2. Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA.
  • 3. Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA.
  • 4. Department of Medicine, University of Southern California, Los Angeles, CA.
  • 5. USC Stem Cell, University of Southern California, Los Angeles, CA.
PMID: 34402812 DOI: 10.1083/jcb.202010118
Abstract

Membrane-bound factors expressed by niche stromal cells constitute a unique class of localized cues and regulate the long-term functions of adult stem cells, yet little is known about the underlying mechanisms. Here, we used a supported lipid bilayer (SLB) to recapitulate the membrane-bound interactions between hematopoietic stem cells (HSCs) and niche stromal cells. HSCs cluster membrane-bound stem cell factor (mSCF) at the HSC-SLB interface. They further form a polarized morphology with aggregated mSCF under a large protrusion through a synergy with VCAM-1 on the bilayer, which drastically enhances HSC adhesion. These features are unique to mSCF and HSCs among the factors and hematopoietic populations we examined. The mSCF-VCAM-1 synergy and the polarized HSC morphology require PI3K signaling and cytoskeletal reorganization. The synergy also enhances nuclear retention of FOXO3a, a crucial factor for HSC maintenance, and minimizes its loss induced by soluble SCF. Our work thus reveals a unique role and signaling mechanism of membrane-bound factors in regulating stem cell morphology and function.

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