ECM Architecture-Mediated Regulation of ß-Cell Differentiation from hESCs via Hippo-Independent YAP Activation.
ACS Biomater Sci Eng
; 9(2): 680-692, 2023 02 13.
Article
em En
| MEDLINE
| ID: mdl-36580628
ABSTRACT
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 α3-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.
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Embrionárias Humanas
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article