Activation of the RhoA-YAP-β-catenin Signaling Axis Promotes the Expansion of Inner Ear Progenitor Cells in 3D Culture,STEM CELLS

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Activation of the RhoA-YAP-β-catenin Signaling Axis Promotes the Expansion of Inner Ear Progenitor Cells in 3D Culture
STEM CELLS ( IF 4.0 ) Pub Date : 2020-03-26 , DOI: 10.1002/stem.3175
Mingyu Xia _{1,

2} , Yan Chen _{1,

2} , Yingzi He _{1,

2} , Huawei Li _{1,

2,

3,

4,

5} , Wenyan Li _{1,

2}

Affiliation

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.

中文翻译：

RhoA-YAP-β-连环蛋白信号轴的激活促进 3D 培养中内耳祖细胞的扩增

细胞机械转导在许多细胞类型的发育和分化中发挥着重要作用，但来自细胞外基质 (ECM) 的机械信号是否以及如何影响内耳祖细胞 (IEPC) 的命运决定仍然很大程度上未知。在目前的研究中，我们比较了 IEPC 在基于 Matrigel 的悬浮和封装培养系统中的生物学行为，我们发现来自 ECM 的机械信号促进了 IEPC 的存活和扩展。此外，我们发现来自 ECM 的机械信号诱导 Ras 同源家族成员 A (RhoA) 的积累，并导致 IEPC 中肌动蛋白细胞骨架的聚合。这些变化反过来导致 Yes 相关蛋白 (YAP) 核定位增加和 IEPC 扩增增强，至少部分通过上调经典的 Wnt 信号通路。因此，我们首次证明 RhoA-YAP-β-catenin 信号轴感知和转导来自 ECM 的机械信号，并在促进 IEPC 的扩展中发挥关键作用。

更新日期：2020-03-26

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