Open AccessActivation of the RhoA‐YAP‐β‐catenin signaling axis promotes the expansion of inner ear progenitor cells in 3D culture
Author(s) -
Xia Mingyu,
Chen Yan,
He Yingzi,
Li Huawei,
Li Wenyan
Publication year - 2020
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.3175
Subject(s) - rhoa , microbiology and biotechnology , biology , extracellular matrix , mechanotransduction , wnt signaling pathway , progenitor cell , matrigel , signal transduction , actin cytoskeleton , catenin , progenitor , inner ear , cytoskeleton , stem cell , cell culture , anatomy , cell , genetics
Cellular mechanotransduction plays an essential role in the development and differentiation of many cell types, but if and how mechanical cues from the extracellular matrix (ECM) influence the fate determination of inner ear progenitor cells (IEPCs) remains largely unknown. In the current study, we compared the biological behavior of IEPCs in Matrigel‐based suspension and encapsulated culture systems, and we found that the mechanical cues from the ECM promote the survival and expansion of IEPCs. Furthermore, we found that the mechanical cues from the ECM induced the accumulation of Ras homolog family member A (RhoA) and caused the polymerization of actin cytoskeleton in IEPCs. These changes in turn resulted in increased Yes‐associated protein (YAP) nuclear localization and enhanced expansion of IEPCs, at least partially through upregulating the canonical Wnt signaling pathway. We therefore provide the first demonstration that the RhoA‐YAP‐β‐catenin signaling axis senses and transduces mechanical cues from the ECM and plays crucial roles in promoting the expansion of IEPCs.