A spatiotemporal atlas of mouse liver homeostasis and regeneration
Open accessAbstract
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.
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A pericentral-to-periportal gradient of Rspo3 in HSCs was observed.
“Consistent with previous studies31–33 and befitting the zonal alterations in HSC-depleted livers, we observed a pericentral-to-periportal gradient of Rspo3 in HSCs (Fig. 3f).”
From Hepatic stellate cells control liver zonation, size and functions via R-spondin 3 (2025) · cites this paper as [33]
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haoshijie13/LISTA: LISTA_code_V1
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Spatiotemporal omics for biology and medicine
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- Authors
- Xu, J., Guo, P., Hao, S., Shangguan, S., Shi, Q., Volpe, G., Huang, K., Zuo, J., An, J., Yuan, Y., Cheng, M., Deng, Q., Zhang, X., Lai, G., Nan, H., Wu, B., Shentu, X., Wu, L., Wei, X., Jiang, Y., Huang, X., Pan, F., Song, Y., Li, R., Wang, Z., Liu, C., Liu, S., Li, Y., Yang, T., Xu, Z., Du, W., Li, L., Ahmed, T., You, K., Dai, Z., Li, L., Qin, B., Li, Y., Lai, L., Qin, D., Chen, J., Fan, R., Li, Y., Hou, J., Ott, M., Sharma, A. D., Cantz, T., Schambach, A., Kristiansen, K., Hutchins, A. P., Göttgens, B., Maxwell, P. H., Hui, L., Xu, X., Liu, L., Chen, A., Lai, Y., & Esteban, M. A.
- Affiliations
- BGI Research (CN)
- BGI Group (China) (CN)
- Chinese Academy of Sciences (CN)
- Guangzhou Institutes of Biomedicine and Health (CN)
- University of Copenhagen (DK)
- Istituto Tumori Bari (IT)
- Chulalongkorn University (TH)
- University of Science and Technology of China (CN)
- Jilin University (CN)
- Shanxi Medical University (CN)
- Nanfang Hospital (CN)
- Medizinische Hochschule Hannover (DE)
- Boston Children's Hospital (US)
- Southern University of Science and Technology (CN)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Cambridge (GB)
- Corresponding author
- Guo, Pengcheng
- Xu, Xun
- Liu, Longqi
- Chen, Ao
- Lai, Yiwei
- Esteban, Miguel A.
- ORCID
- Xu, Jiangshan
- Hao, Shijie
- Shi, Quan
- Volpe, Giacomo
- Huang, Keke
- An, Juan
- Yuan, Yue
- Deng, Qiuting
- Zhang, Xiao
- Wu, Baihua
- Wu, Liang
- Wei, Xiaoyu
- Jiang, Yujia
- Huang, Xin
- Li, Ronghai
- Wang, Zhifeng
- Liu, Chuanyu
- Liu, Shiping
- Li, Yuxiang
- Yang, Tao
- Xu, Zhicheng
- Li, Ling
- Ahmed, Tanveer
- You, Kai
- Dai, Zhen
- Li, Li
- Qin, Baoming
- Li, Yinxiong
- Lai, Liangxue
- Qin, Dajiang
- Chen, Junling
- Fan, Rong
- Hou, Jinlin
- Ott, Michael
- Sharma, Amar Deep
- Cantz, Tobias
- Schambach, Axel
- Kristiansen, Karsten
- Hutchins, Andrew P.
- Göttgens, Berthold
- Maxwell, Patrick H.
- Hui, Lijian
- Xu, Xun
- Liu, Longqi
- Chen, Ao
- Lai, Yiwei
- Esteban, Miguel A.
- Venue
- Nature Genetics
- Published
- 2024-04-16
- Volume
- 56
- Issue
- 5
- Pages
- 953-969
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W4394845803
- Cited by
- 75
- References
- 91
- Citations by year
- 2026: 29 · 2025: 36 · 2024: 10
- FWCI
- 19.63
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- National Natural Science Foundation of China (32200688, 92168202, 32370848)
- Medical Research Council (MC_PC_17230)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- liver homeostasis, liver regeneration, mouse liver, spatiotemporal atlas, Stereo-seq, single-cell transcriptomics, partial hepatectomy, hepatocyte proliferation, TBL1XR1, Wnt/β-catenin signaling, inflammation, intercellular communication, gene regulatory networks, cell-cell interactions
- MeSH terms
- Animals, Homeostasis, Liver, Liver Regeneration, Male, Mice, Inbred C57BL, Receptors, Cytoplasmic and Nuclear, Gene Expression Profiling, Hepatocytes, Cell Proliferation, Mice, Gene Regulatory Networks, Single-Cell Analysis, Transcriptome, Wnt Signaling Pathway
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