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bioRxiv · 10.1101/2022.02.06.479312

Fate tracing reveals differences between Reelin+ HSCs and Desmin+ HSCs in activation, migration, and proliferation activities

Chen, N.·Liu, S.·Qin, D.·Guan, D.·Chen, Y.·Hou, C.·Zheng, S.·Wang, L.·Chen, X.·Zhang, L.
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Abstract

The activation of hepatic stellate cells (HSCs) which comprise distinct clusters, is the main cause of liver fibrogenesis in response to different etiologies of chronic liver injuries. In this study, we constructed a novel ReelinCreERT2 transgenic mouse in which cells expressing Reelin were fully marked and demonstrated that about 50% HSCs were labeled. These ReelinCreERT2-labeled HSCs displayed distinct characteristics in migration, activation and proliferation compared to Desmin+ HSCs (total HSCs) in cholestatic (bile duct ligation; BDL) or hepatotoxic (carbon tetrachloride; CCl4) liver injuries. In BDL-induced fibrotic livers, Desmin+ HSCs were activated with increased proliferation and accumulation activities around the portal triad, but mGFP+ HSCs did not show proliferation or accumulation activity around the portal triad, and only a small part was activated. In CCl4-induced fibrotic livers, most of Desmin+ and mGFP+ HSCs were activated along with proliferation and accumulation potential around the central vein, however fewer mGFP+ HSCs were activated compared to Desmin+ HSCs. Moreover, in the regression of CCl4-induced fibrosis, mGFP+ HSCs were apoptosed whereas Desmin+ HSCs recovered to normal state. Besides, we didnt find evidence that mGFP+ HSCs transdifferentiated into hepatocytes or cholangiocytes through mesenchymal-epithelial transition (MET).

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Chen, N., Liu, S., Qin, D., Guan, D., Chen, Y., Hou, C., Zheng, S., Wang, L., Chen, X., Zhang, L.. 2022-02-09. Fate tracing reveals differences between Reelin+ HSCs and Desmin+ HSCs in activation, migration, and proliferation activities. https://doi.org/10.1101/2022.02.06.479312

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