title: Dynamics of Mechanosensitive Neural Stem Cell Differentiation.
abstract: 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.
authors: Department of Bioengineering, University of California, Berkeley, California, , USA.|Department of Chemical and Biomolecular Engineering, University of California, Berkeley, California, USA.
authors: Sebastian
authors: S
authors: Rammensee
authors: UC Berkeley - UCSF Joint Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, California, USA.
authors: Michael S
authors: MS
authors: Kang
authors: Department of Chemical and Biomolecular Engineering, University of California, Berkeley, California, USA.
authors: Katerina
authors: K
authors: Georgiou
authors: Department of Bioengineering, University of California, Berkeley, California, , USA.|Department of Chemical and Biomolecular Engineering, University of California, Berkeley, California, USA.|UC Berkeley - UCSF Joint Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, California, USA.
authors: Sanjay
authors: S
authors: Kumar
authors: Department of Bioengineering, University of California, Berkeley, California, , USA.|Department of Chemical and Biomolecular Engineering, University of California, Berkeley, California, USA.|UC Berkeley - UCSF Joint Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, California, USA.
authors: David V
authors: DV
authors: Schaffer
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002454:Cell Differentiation; D019070:Cell Lineage; D040542:Mechanotransduction, Cellular; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D055495:Neurogenesis; D051381:Rats; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051176:beta Catenin
keywords: Adult stem cells; Neural differentiation; Neural stem cell; Progenitor cells; Stem cell-microenvironment interactions; Wnt Signaling; Yes-associated protein