吉林大学Miguel A. Esteban等研究人员合作绘制出小鼠肝脏稳态和再生的时空图谱。2024年4月16日，《自然—遗传学》杂志在线发表了这项成果。

研究人员将Stereo-seq（时空增强分辨的组学测序）与473290个细胞的单细胞转录组分析相结合，在全叶尺度上生成了小鼠肝脏稳态和再生的高分辨率时空图谱。该综合研究详细剖析了控制肝细胞功能的分子梯度，系统地定义了基因网络如何通过细胞间通信动态调节以促进再生。

在其他重要的调节因子中，研究人员发现转录辅助因子TBL1XR1是连接炎症与Wnt/β-catenin信号的变阻器，可促进肝细胞增殖。这些数据和分析管线，为未来器官生理和功能失调的高清组织尺度图谱奠定了基础。

据介绍，人们对哺乳动物肝细胞在组织稳态和扰动过程中协调反应的机制知之甚少，这是人们了解许多疾病的主要障碍。造成这一知识空白的原因是，研究不同状态和位置的多种细胞类型非常困难，尤其是当这些细胞类型是瞬时的时候。

附：英文原文

Title: A spatiotemporal atlas of mouse liver homeostasis and regeneration

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

Issue&Volume: 2024-04-16

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.

DOI: 10.1038/s41588-024-01709-7

Source: https://www.nature.com/articles/s41588-024-01709-7