ECM Architecture-Mediated Regulation of fl-Cell Differentiation from hESCs via Hippo-Independent YAP Activation

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Changes in the extracellular matrix (ECM) influence stem cell fate. When hESCs were differentiated on a thin layer of Matrigel coated onto PDMS (Matrigel_PDMS), they exhibited a substantial increase in focal adhesion and focal adhesion-associated proteins compared with those cultured on Matrigel coated onto TCPS (Matrigel_TCPS), resulting in YAP/TEF1 activation and ultimately promoting the transcriptional activities of pancreatic endoderm (PE)-associated genes. Interestingly, YAP activation in PE cells was mediated through integrin alpha 3-FAK-CDC42-PP1A signaling rather than the typical Hippo signaling pathway. Furthermore, pancreatic islet-like organoids (PIOs) generated on Matrigel_PDMS secreted more insulin than those generated from Matrigel_TCPS. Electron micrographs revealed differential Matrigel architectures depending on the underlying substrate, resulting in varying cell matrix anchorage resistance levels. Accordingly, the high apparent stiffness of the unique mucus-like network structure of Matrigel_PDMS was the critical factor that directly upregulated focal adhesion, thereby leading to better maturation of the pancreatic development of hESCs in vitro.
Publisher
AMER CHEMICAL SOC
Issue Date
2023-02
Language
English
Article Type
Article
Citation

ACS BIOMATERIALS SCIENCE & ENGINEERING, v.9, no.2, pp.680 - 692

DOI
10.1021/acsbiomaterials.2c01054
URI
http://hdl.handle.net/10203/305173
Appears in Collection
ME-Journal Papers(저널논문)MSE-Journal Papers(저널논문)
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