A single-cell fixed RNA profiling of liver fibrosis progression and regression reveals SEMA4D and LMCD1 as key mediators of fibrogenesis
Pham, D. M.; Thuy, L. T. T.; Hoang, H.; Nguyen, H. T.; Pham, A. T.; Ikenaga, H.; Fuji, H.; Yuasa, H.; Matsubara, T.; Vu, H. T.; Yi, C.; Yamagishi, R.; Ohtani, N.; Oikawa, D.; Tokunaga, F.; Kisseleva, T.; Brenner, D.; Iwakiri, Y.; Sancho, J. G.; Kawada, N.
Show abstract
Liver fibrosis progression and regression are dynamic processes involving diverse hepatic and immune cell populations. Here, we utilize single-cell fixed RNA profiling (FLEX) of a TAA-induced mouse liver cirrhosis model, with and without a recovery phase, to depict the cellular landscape and molecular mechanisms of fibrosis resolution. The regression phase was characterized by the emergence of pericentral hepatocytes enriched in detoxification and antioxidant genes (e.g., Cyp2e1, Txn1), which secreted Rarres2 to modulate hepatic stellate cell (HSC) function. This was accompanied by the upregulation of scar-resolving genes (Mmp14, Ctsl), restoration of fenestrae in liver sinusoidal endothelial cells, anti-inflammatory phenotypes of Kupffer cells, a decrease in fibrogenic cholangiocyte subsets, and recovery-associated signatures in NK/T cells, B cells, and neutrophils. In contrast, SEMA4D secreted by monocyte-derived macrophages during fibrosis progression activated Plxnb2 HSCs, and its blockade attenuated fibrosis in vivo. Furthermore, LMCD1 was identified as a novel marker for HSC activation and regulation. This single-cell atlas reveals key transcriptional programs and intercellular signaling pathways dependent on the fibrotic condition, offering new therapeutic targets for liver cirrhosis.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Liver Sinusoidal Endothelial Cells and Laminin dictate cholangiocytes fate in chronic liver disease 96%
- 24-Nor-Ursodeoxycholic acid reshapes immunometabolism in CD8+ T cells and alleviates hepatic inflammation 94%
- Hepatocyte Dedifferentiation Profiling In Alcohol-Related Liver Disease Identifies CXCR4 As A Driver Of Cell Reprogramming 94%
Similar papers in this journal
- Systemic identification of functionally conserved lncRNA metabolic regulators in human and mouse livers 94%
- Tofacitinib uptake by patient-derived intestinal organoids predicts individual clinical responsiveness 94%
- Single nucleus and in situ RNA sequencing reveals cell topographies in the human pancreas 93%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.