Region-specific cellular and molecular basis of liver regeneration after acute pericentral injury.
Open accessAbstract
Liver injuries often occur in a zonated manner. However, detailed regenerative responses to such zonal injuries at cellular and molecular levels remain largely elusive. By using a fate-mapping strain, Cyp2e1-DreER, to elucidate liver regeneration after acute pericentral injury, we found that pericentral regeneration is primarily compensated by the expansion of remaining pericentral hepatocytes, and secondarily by expansion of periportal hepatocytes. Employing single-cell RNA sequencing, spatial transcriptomics, immunostaining, and in vivo functional assays, we demonstrated that the upregulated expression of the mTOR/4E-BP1 axis and lactate dehydrogenase A in hepatocytes contributes to pericentral regeneration, while activation of transforming growth factor β (TGF-β1) signaling in the damaged area mediates fibrotic responses and inhibits hepatocyte proliferation. Inhibiting the pericentral accumulation of monocytes and monocyte-derived macrophages through an Arg-Gly-Asp (RGD) peptide-based strategy attenuates these cell-derived TGF-β1 signalings, thus improving pericentral regeneration. Our study provides integrated and high-resolution spatiotemporal insights into the cellular and molecular basis of pericentral regeneration.
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Acute Pericentral Liver Injury Induces a Novel Transient Hepatocyte PopulationPreprint
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Activation and Spatial Redistribution of RNA Splicing Factors Trigger Hepatic Regeneration
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Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injuryPreprint
Zhu, Y., Deng, C., Chen, B., He, J., Liu, Y., Lei, S., Lu, W., Peng, C., & Shan, Z. (2025) · eLife · doi:10.7554/elife.108646
Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injuryPreprint
Zhu, Y., Deng, C., Chen, B., He, J., Liu, Y., Peng, C., & Shan, Z. (2025) · eLife · doi:10.7554/elife.108646.1
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Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injuryPreprint
Zhu, Y., Deng, C., Chen, B., He, J., Liu, Y., Lei, S., Lu, W., Peng, C., & Shan, Z. (2026) · eLife · doi:10.7554/elife.108646.3
- Authors
- Wang, S., Wang, X., Shan, Y., Tan, Z., Su, Y., Cao, Y., Wang, S., Dong, J., Gu, J., & Wang, Y.
- Affiliations
- Chinese PLA General Hospital (CN)
- Beijing Tsinghua Chang Gung Hospital (CN)
- Tsinghua University (CN)
- Institute of Health Service and Transfusion Medicine (CN)
- Beijing National Research Center for Information Science and Technology (CN)
- Corresponding author
- Gu, Jin
- Wang, Yunfang
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2024-03
- Volume
- 31
- Issue
- 3
- Pages
- 341-358.e7
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W4392040118
- Semantic Scholar
- 669e2d194c2742b305e30fc41a4abaa123a8d048
- Cited by
- 40
- References
- 66
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 6 · 2023: 1
- FWCI
- 8.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 371 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key Research and Development Program of China (2021YFF1200901)
- Beijing Municipal Natural Science Foundation
- Natural Science Foundation of Beijing Municipality (82090053, 81930119, 92268104, 81730052, 7222182)
- National Natural Science Foundation of China (32100694, 92168207)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- liver regeneration, hepatocyte proliferation, LDHA, TGF-β1 signaling, liver fibrosis, monocyte-derived macrophages, RGD peptide
- MeSH terms
- Liver, Liver Regeneration, Hepatocytes, Cell Proliferation, Transforming Growth Factor beta1
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