Project description:Purpose: Mechanical homeostasis is a crucial process for endothelial cell (EC) survival and functionality. Cells can sense environmental change and modify the expression of extracellular matrix, focal adhesion and cytoskeleton protein to maintain the correct mechanical homeostasis. In this study, we observed change in microRNA levels linked with mechanical response. ECs were seeded for 48 hour on PDMS 3 kPa and 30 kPa substrate coating with fibronectin to simulate "soft" and "stiff" substrate, then sRNA-seq was performed.
Project description:Purpose: mechanical homeostasis is a crucial process for Humen dermal fibroblast cell (HDFs) survival and functionality. Cell can sense environmental change and modify the expression of extracellular matrix, focal adhesion and cytoskeleton protein to maintain the correct mechanical homeostasis. In this study we observed change in microRNA levels linked with mechanical response. HDFs were seeded for 48 our on PDMS 3 kPa and 30 kPa substrate coating with fibronectin to simulate "soft" and "stiff" substrate, then sRNA-seq was performed.
Project description:Purpose: Mechanical homeostasis is a crucial process for endothelial cell (EC) survival and functionality. Cells can sense environmental change and modify the expression of extracellular matrix, focal adhesion and cytoskeleton protein to maintain the correct mechanical homeostasis. In this study, we observed change in mRNA levels linked with mechanical response. ECs were seeded for 48 hour on PDMS 3 kPa and 30 kPa substrate coating with fibronectin to simulate "soft" and "stiff" substrate, then RNA-seq was performed.
Project description:Here, we applied single-cell RNA seq to uncover the heterogeneity of endothelial cells (ECs) under different stiffness and TGF-β induction. We identified three distinct EC clusters that was consistenyl showed in all different conditions . Further subclustering analysis revealed finer heterogeneity which were differentially impacted by stiffness and TGF-β.
Project description:Tumor progression is often accompanied with increased extracellular matrix stiffness, but how this affects endothelial cells (ECs) is largely unknown. We used mass spectrometry to analyse the proteomic changes of primary human ECs cultured on physiological or tumor stiffness and found that CCN1/CYR61 is highly induced by tumor stiffness. Knock out of Ccn1 in the vasculature of Ccn1loxP/loxP mice by administrating a soluble form of Cre shows that fewer of the treated mice harbour circulating tumor cells and lung metastases, without affecting primary tumor growth, using the B16F10 syngeneic mouse melanoma model This demonstrates that CCN1 loss in the host impairs cancer metastasis and we dissected the molecular mechanism in vitro. Stiffness-induced CCN1 acts via (integrin αvβ3), FAK, beta-catenin signalling to increase N-Cadherin expression in ECs, which, in turn, leads to an elevated adhesion of cancer cells to ECs via N-Cadherin homophilic interactions.