Membrane-bound SCF and VCAM-1 synergistically regulate the morphology of hematopoietic stem cells.
Membrane-bound SCF and VCAM-1 synergistically regulate the morphology of hematopoietic stem cells.
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DOI：
10.1083/jcb.202010118
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发表时间：
2021-10-04
期刊：
影响因子：
--
通讯作者：
Shen K
中科院分区：
文献类型：
--
作者：
Hao J;Zhou H;Nemes K;Yen D;Zhao W;Bramlett C;Wang B;Lu R;Shen K
造血干细胞形成极化形态，膜结合SCF上的FOXO3a和脂质双分子层上的VCAM-1的黏附增强和核改善。这项工作揭示了小生境膜结合因子在干细胞锚定和维持中的独特作用。由小生境基质细胞表达的膜结合因子构成了一类独特的局部信号，并调节成体干细胞的长期功能，但对其潜在机制知之甚少。在这里，我们使用支持脂质双分子层（SLB）来概括造血干细胞（hsc）和小生境基质细胞之间的膜结合相互作用。造血干细胞聚集膜结合干细胞因子（mSCF）在造血干细胞- slb界面。它们通过与双分子层上的VCAM-1协同作用，进一步与聚集在一起的mSCF形成大突起的极化形态，从而显著增强HSC的粘附。这些特征是mSCF和hsc在我们所研究的因素和造血群体中所特有的。mSCF-VCAM-1协同作用和HSC极化形态需要PI3K信号和细胞骨架重组。这种协同作用还增强了FOXO3a的核保留，这是维持HSC的关键因素，并最大限度地减少了可溶性SCF引起的FOXO3a的损失。因此，我们的工作揭示了膜结合因子在调节干细胞形态和功能中的独特作用和信号传导机制。
Hematopoietic stem cells form a polarized morphology with enhanced adhesion and improved nuclear FOXO3a on membrane-bound SCF and VCAM-1 on a lipid bilayer. The work reveals a unique role of the niche membrane-bound factors in stem cell anchorage and maintenance. 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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影响因子：
23.9
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Scadden, David