Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
ACS Biomater Sci Eng. 2023 Feb 13;9(2):680-692. doi: 10.1021/acsbiomaterials.2c01054. Epub 2022 Dec 29.
Changes in the extracellular matrix (ECM) influence stem cell fate. When hESCs were differentiated on a thin layer of Matrigel coated onto PDMS (Matrigel_), they exhibited a substantial increase in focal adhesion and focal adhesion-associated proteins compared with those cultured on Matrigel coated onto TCPS (Matrigel_), 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_ secreted more insulin than those generated from Matrigel_. 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_ was the critical factor that directly upregulated focal adhesion, thereby leading to better maturation of the pancreatic development of hESCs .
细胞外基质（ECM）的变化会影响干细胞的命运。当 hESC 在涂有 Matrigel 的 PDMS（Matrigel_）薄层上分化时，与在涂有 Matrigel 的 TCPS（Matrigel_）上培养的细胞相比，它们的黏着斑和黏着斑相关蛋白显著增加，导致 YAP/TEF1 激活，最终促进胰腺内胚层（PE）相关基因的转录活性。有趣的是，PE 细胞中的 YAP 激活是通过整合素 α3-FAK-CDC42-PP1A 信号通路而不是典型的 Hippo 信号通路介导的。此外，在 Matrigel_上生成的胰岛样类器官（PIOs）比在 Matrigel 上生成的 PIOs 分泌更多的胰岛素。电子显微镜照片显示，根据不同的基底，Matrigel 有不同的结构，导致细胞-基质附着阻力水平的变化。因此，Matrigel_独特的黏液样网络结构的高表观硬度是直接上调黏着斑的关键因素，从而导致 hESC 的胰腺发育更好地成熟。
