Cholestatic Injury and Repair Spatio-Temporal Atlas
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Summary:
Cholestatic injuries, characterized by regional damage around the periportal region, lack curative therapies and cause considerable mortality. In this study, we generated a high-definition spatiotemporal atlas during cholestatic injury and repair by Stereo-seq and single-cell transcriptomics. We uncovered that cholangiocytes function as a periportal hub (cholangio-hub) by integrating multiple signals with neighboring cells. Feedback between cholangiocytes and lipid-associated macrophages (LAM) was detected in the cholangio-hub, which is related to the differentiation of LAM, a recently identified subpopulation of macrophages crucial in tissue injury. Moreover, the cholangio-hub highly expressed TGFβ, which is associated with cholangiocyte conversion of liver progenitor-like cells during injury and dampened proliferation of periportal hepatocytes during recovery. Importantly, spatiotemporal analysis revealed a key inhibitory rheostat for hepatocyte proliferation. Our data provide a comprehensive resource for demarcating regional cholestatic injuries.Overall design:
We collected C57BL/6 mouse livers during DDC injury and withdrawal at six time points,
107 normal livers (day 0 before DDC treatment, D0), DDC-damaged livers at days 8 and
108 17 (D8 and D17), livers at recovery days 2, 7 and 21 (R2, R7, and R21)Technology:
Stereo-Seq
Platform:
DNBseq
Species:
Mus musculus
Tissues:
Liver
Cell types:
Hepatocyte, Cholangiocyte, Monocyte, Macrophage, Fibroblast, Hepatic Stellate cell, Kupffer, Liver Sinusoidal Endothelial Cell, B cell, T cell, Liver progenitor like cell, Liver Vessel Endothelial Cell
Submission date: 2024-03-22Update date: 2024-03-22
Sample number: 50Section number: 22
Contributors
Shijie Hao
Contact: haoshijie@genomics.cn
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