中国科学院分子细胞科学卓越创新中心周斌等研究人员合作发现，双潜能过渡性肝脏祖细胞贡献于肝脏再生。这一研究成果于2023年3月13日在线发表在国际学术期刊《自然—遗传学》上。

研究人员确定了一种过渡性肝脏祖细胞（TLPC），它起源于胆汁上皮细胞（BEC），并在严重肝损伤的再生过程中分化为肝细胞。通过应用双基因系追踪方法，研究人员特异性地标记了TLPC，并发现它们是双潜能性的，因为它们要么分化成肝细胞，要么重新接受BEC的命运。在机制上，Notch和Wnt/β-catenin信号分别协调了BEC到TLPC和TLPC到肝细胞的转换。总之，这项研究为转分化辅助肝脏再生提供了功能和机制上的见解。

研究人员表示，严重的肝脏损伤后，当肝细胞介导的再生受损时，BEC可以转分化为功能性肝细胞。然而，具有这种潜在组织干细胞潜力的BEC亚群，以及实现转分化的机制，仍然难以捉摸。

附：英文原文

Title: Bipotent transitional liver progenitor cells contribute to liver regeneration

Author: Pu, Wenjuan, Zhu, Huan, Zhang, Mingjun, Pikiolek, Monika, Ercan, Caner, Li, Jie, Huang, Xiuzhen, Han, Ximeng, Zhang, Zhenqian, Lv, Zan, Li, Yan, Liu, Kuo, He, Lingjuan, Liu, Xiuxiu, Heim, Markus H., Terracciano, Luigi M., Tchorz, Jan S., Zhou, Bin

Issue&Volume: 2023-03-13

Abstract: Following severe liver injury, when hepatocyte-mediated regeneration is impaired, biliary epithelial cells (BECs) can transdifferentiate into functional hepatocytes. However, the subset of BECs with such facultative tissue stem cell potential, as well as the mechanisms enabling transdifferentiation, remains elusive. Here we identify a transitional liver progenitor cell (TLPC), which originates from BECs and differentiates into hepatocytes during regeneration from severe liver injury. By applying a dual genetic lineage tracing approach, we specifically labeled TLPCs and found that they are bipotent, as they either differentiate into hepatocytes or re-adopt BEC fate. Mechanistically, Notch and Wnt/β-catenin signaling orchestrate BEC-to-TLPC and TLPC-to-hepatocyte conversions, respectively. Together, our study provides functional and mechanistic insights into transdifferentiation-assisted liver regeneration.

DOI: 10.1038/s41588-023-01335-9

Source: https://www.nature.com/articles/s41588-023-01335-9