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.

中文翻译：

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膜结合的SCF和VCAM-1协同调节造血干细胞的形态

由生态位基质细胞表达的膜结合因子构成一类独特的局部线索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，我们使用支持的脂质双层（SLB）来概括造血干细胞（HSC）和生态位基质细胞之间的膜结合相互作用。HSC 在 HSC-SLB 界面聚集膜结合干细胞因子 (mSCF)。通过与双层上的 VCAM-1 协同作用，它们进一步在大突起下形成聚集的 mSCF 的极化形态，从而大大增强 HSC 粘附。在我们检查的因子和造血群体中，这些特征是 mSCF 和 HSC 所独有的。mSCF-VCAM-1 协同作用和极化 HSC 形态需要 PI3K 信号传导和细胞骨架重组。这种协同作用还增强了 FOXO3a 的核保留（HSC 维持的关键因素），并最大限度地减少了可溶性 SCF 引起的损失。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机制。