机械敏感通道
神经科学
机械转化
神经球
间充质干细胞
细胞
细胞命运测定
电池类型
作者
Sebastian Rammensee,Michael S. Kang,Katerina Georgiou,Sanjay Kumar,David V. Schaffer
出处
期刊:Stem Cells
[Wiley]
日期:2017-02-01
卷期号:35 (2): 497-506
被引量:74
摘要
Stem cell differentiation can be highly sensitive to mechanical inputs from the extracellular matrix (ECM). Identifying temporal windows during which lineage commitment responds to ECM stiffness, and the signals that mediate these decisions, would advance both mechanistic insights and translational efforts. To address these questions, we investigate adult neural stem cell (NSC) fate commitment using an oligonucleotide-crosslinked ECM platform that for the first time offers dynamic and reversible control of stiffness. Stiffness pulse studies in which the ECM was transiently or permanently softened or stiffened at specified initiation times and durations pinpoint a 24-hour window in which ECM stiffness maximally impacts neurogenic commitment. Overexpression of the transcriptional coactivator Yes-associated protein (YAP) within this window suppressed neurogenesis, and silencing YAP enhanced it. Moreover, ablating YAP-β-catenin interaction rescued neurogenesis. This work reveals that ECM stiffness dictates NSC lineage commitment by signaling via a YAP and β-catenin interaction during a defined temporal window. Stem Cells 2017;35:497-506.
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