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Characterization and identification of hepatic mesenchymal stromal cell populations Tausan, Daniel

Abstract

Mesenchymal stromal or stem cells (MSCs) play central roles in numerous physiological processes including tissue development, regeneration and homeostasis. In this study, the homeostatic properties of hepatic MSC’s were characterized by next generation sequencing (NGS) technology at single cell resolution. Hic1 (Hypermethylated in Cancer 1) was found to be a systemic marker of MSCs, and mouse models incorporating a CreERT2 knock-in into this locus were used to genetically trace and characterize labeled hepatic MSCs (HMSCs). Three hepatic mesenchymal cell types were marked by Hic1-expression, the vitamin A storing hepatic stellate cells (HSC), portal fibroblasts (PF) and the hepatic capsule lining mesothelial cell (MC). These HMSCs were known to contribute to regeneration and renewal, and herein data is provided to show that Hic1-expressing cells proliferate in response to liver injury and acquire a pro-regenerative myofibroblastic-like phenotype. Additionally, analysis of Hic1-lineage marked cells from liver with single cell RNA-seq showed that the liver sinusoidal endothelial cell (LSEC) compartment also appeared to be labelled. Hic1-expression within LSECs remains inconclusive and requires further investigation. No marker to date has captured the full spectrum of HMSCs making Hic1 a unique candidate to study the liver stroma.

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Attribution-NonCommercial-NoDerivatives 4.0 International

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