美国德克萨斯大学Hao Zhu研究组发现，表达IGFBP2的中叶肝细胞优先贡献于肝脏稳态和再生。相关论文发表在2023年5月4日出版的《细胞—干细胞》杂志上。

研究人员产生了一个Igfbp2-CreER基因敲入品系，专门标记中叶肝细胞。在1年的稳态过程中，第2区肝细胞的丰度发生增加，直至占据小叶面积的21%-41%。在用四氯化碳损伤中央静脉周围或用3,5-二乙氧基羰基-1,4-二氢吡啶（DDC）损伤门静脉周围后，IGFBP2⁺细胞分别补充了第3区和第1区丢失的肝细胞。IGFBP2⁺细胞也优先促进了70%部分肝切除术后的再生，以及怀孕期间的肝脏生长。由于IGFBP2的标记随着禁食而大幅增加，研究人员使用单核转录组学来探索作为营养功能的分区，并发现分区的分工随着禁食而急剧转变。

这些研究证明了IGFBP2标记的第2区肝细胞对肝脏平衡和再生的贡献。

据悉，虽然第2区的中叶肝细胞是最近确定的肝脏稳态和再生的细胞来源，但这些细胞还没有被专门绘制命运图谱。

附：英文原文

Title: IGFBP2 expressing midlobular hepatocytes preferentially contribute to liver homeostasis and regeneration

Author: Yu-Hsuan Lin, Yonglong Wei, Qiyu Zeng, Yunguan Wang, Chase A. Pagani, Lin Li, Min Zhu, Zixi Wang, Meng-Hsiung Hsieh, Natasha Corbitt, Yu Zhang, Tripti Sharma, Tao Wang, Hao Zhu

Issue&Volume: 2023/05/04

Abstract: Although midlobular hepatocytes in zone 2 are a recently identified cellular sourcefor liver homeostasis and regeneration, these cells have not been exclusively fatemapped. We generated an Igfbp2-CreER knockin strain that specifically labels midlobular hepatocytes. During homeostasisover 1 year, zone 2 hepatocytes increased in abundance from occupying 21%–41% of thelobular area. After either pericentral injury with carbon tetrachloride or periportalinjury with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), IGFBP2+ cells replenishedlost hepatocytes in zones 3 and 1, respectively. IGFBP2+ cells also preferentiallycontributed to regeneration after 70% partial hepatectomy, as well as liver growthduring pregnancy. Because IGFBP2 labeling increased substantially with fasting, weused single nuclear transcriptomics to explore zonation as a function of nutrition,revealing that the zonal division of labor shifts dramatically with fasting. Thesestudies demonstrate the contribution of IGFBP2-labeled zone 2 hepatocytes to liverhomeostasis and regeneration.

DOI: 10.1016/j.stem.2023.04.007

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00125-X