期刊
STEM CELLS
卷 35, 期 2, 页码 497-506出版社
WILEY-BLACKWELL
DOI: 10.1002/stem.2489
关键词
Neural stem cell; Neural differentiation; Stem cell-microenvironment interactions; Adult stem cells; Progenitor cells; Yes-associated protein; Wnt Signaling
资金
- California Institute for Quantitative Biosciences
- California Institute for Regenerative Medicine through the CIRM/QB3 Shared Stem Cell Facility
- NIH [1R01NS074831]
- Human Frontier Science Program
- NSF
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-beta-catenin interaction rescued neurogenesis. This work reveals that ECM stiffness dictates NSC lineage commitment by signaling via a YAP and beta-catenin interaction during a defined temporal window.
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