期刊
JOURNAL OF CELL BIOLOGY
卷 220, 期 10, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.202010118
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资金
- National Institutes of Health [R21EB024748, R01CA220012]
- University of Southern California Viterbi School of Engineering
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Innovation Award
- Rose Hills Foundation fellowship
- STOP CANCER Marni Levine Memorial Research Career Development Award
- Phi Beta Psi Charity Trust
- University of Southern California Provost's PhD Fellowship
- National Institutes of Health National Cancer Institute Award [P30CA014089]
This research demonstrates that membrane-bound factors play a unique role in regulating stem cell morphology and function, uncovering the signaling mechanism involved in the interaction between hematopoietic stem cells and niche stromal cells.
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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