A spatiotemporal atlas of mouse liver homeostasis and regeneration
- PMID: 38627598
- DOI: 10.1038/s41588-024-01709-7
A spatiotemporal atlas of mouse liver homeostasis and regeneration
Abstract
The mechanism by which mammalian liver cell responses are coordinated during tissue homeostasis and perturbation is poorly understood, representing a major obstacle in our understanding of many diseases. This knowledge gap is caused by the difficulty involved with studying multiple cell types in different states and locations, particularly when these are transient. We have combined Stereo-seq (spatiotemporal enhanced resolution omics-sequencing) with single-cell transcriptomic profiling of 473,290 cells to generate a high-definition spatiotemporal atlas of mouse liver homeostasis and regeneration at the whole-lobe scale. Our integrative study dissects in detail the molecular gradients controlling liver cell function, systematically defining how gene networks are dynamically modulated through intercellular communication to promote regeneration. Among other important regulators, we identified the transcriptional cofactor TBL1XR1 as a rheostat linking inflammation to Wnt/β-catenin signaling for facilitating hepatocyte proliferation. Our data and analytical pipelines lay the foundation for future high-definition tissue-scale atlases of organ physiology and malfunction.
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.
Similar articles
-
The Canonical Wnt Pathway as a Key Regulator in Liver Development, Differentiation and Homeostatic Renewal.Genes (Basel). 2020 Sep 30;11(10):1163. doi: 10.3390/genes11101163. Genes (Basel). 2020. PMID: 33008122 Free PMC article. Review.
-
Tissue Repair in the Mouse Liver Following Acute Carbon Tetrachloride Depends on Injury-Induced Wnt/β-Catenin Signaling.Hepatology. 2019 Jun;69(6):2623-2635. doi: 10.1002/hep.30563. Epub 2019 Apr 9. Hepatology. 2019. PMID: 30762896 Free PMC article.
-
Bile acids and their receptors during liver regeneration: "Dangerous protectors".Mol Aspects Med. 2017 Aug;56:25-33. doi: 10.1016/j.mam.2017.03.002. Epub 2017 Mar 23. Mol Aspects Med. 2017. PMID: 28302491 Review.
-
Clustering nuclear receptors in liver regeneration identifies candidate modulators of hepatocyte proliferation and hepatocarcinoma.PLoS One. 2014 Aug 12;9(8):e104449. doi: 10.1371/journal.pone.0104449. eCollection 2014. PLoS One. 2014. PMID: 25116592 Free PMC article.
-
The transforming growth factor-α and cyclin D1 genes are direct targets of β-catenin signaling in hepatocyte proliferation.J Hepatol. 2011 Jul;55(1):86-95. doi: 10.1016/j.jhep.2010.10.021. Epub 2010 Nov 30. J Hepatol. 2011. PMID: 21145869
References
-
- He, L. et al. Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair. Science 371, 6532 (2021). - DOI
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous