A spatiotemporal atlas of mouse liver homeostasis and regeneration

Research output: Contribution to journalJournal articleResearchpeer-review

  • Jiangshan Xu
  • Pengcheng Guo
  • Shijie Hao
  • Shuncheng Shangguan
  • Giacomo Volpe
  • Keke Huang
  • Jing Zuo
  • Juan An
  • Yue Yuan
  • Mengnan Cheng
  • Qiuting Deng
  • Xiao Zhang
  • Guangyao Lai
  • Haitao Nan
  • Baihua Wu
  • Xinyi Shentu
  • Liang Wu
  • Xiaoyu Wei
  • Yujia Jiang
  • Xin Huang
  • Fengyu Pan
  • Yumo Song
  • Ronghai Li
  • Zhifeng Wang
  • Chuanyu Liu
  • Shiping Liu
  • Yuxiang Li
  • Tao Yang
  • Zhicheng Xu
  • Wensi Du
  • Ling Li
  • Tanveer Ahmed
  • Kai You
  • Zhen Dai
  • Li Li
  • Baoming Qin
  • Yinxiong Li
  • Liangxue Lai
  • Dajiang Qin
  • Junling Chen
  • Rong Fan
  • Yongyin Li
  • Jinlin Hou
  • Michael Ott
  • Amar Deep Sharma
  • Tobias Cantz
  • Axel Schambach
  • Andrew P. Hutchins
  • Berthold Göttgens
  • Patrick H. Maxwell
  • Lijian Hui
  • Xun Xu
  • Longqi Liu
  • Yiwei Lai
  • Miguel A. Esteban

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.

Original languageEnglish
JournalNature Genetics
Volume56
Pages (from-to)953-969
Number of pages17
ISSN1061-4036
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

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