IGFBP2 expressing midlobular hepatocytes preferentially contribute to liver homeostasis and regeneration.
IGFBP2 expressing midlobular hepatocytes preferentially contribute to liver homeostasis and regeneration.
复制标题
表达 IGFBP2 的小叶中肝细胞优先促进肝脏稳态和再生。
DOI：
10.1016/j.stem.2023.04.007
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发表时间：
2023
期刊：
影响因子：
23.9
通讯作者：
Zhu,Hao
中科院分区：
文献类型：
--
作者：
Lin,Yu-Hsuan;Wei,Yonglong;Zeng,Qiyu;Wang,Yunguan;Pagani,ChaseA;Li,Lin;Zhu,Min;Wang,Zixi;Hsieh,Meng-Hsiung;Corbitt,Natasha;Zhang,Yu;Sharma,Tripti;Wang,Tao;Zhu,Hao
尽管2区的小叶中肝细胞是最近确定的肝脏稳态和再生的细胞来源，但这些细胞尚未被完全定位。我们产生了特异性标记小叶中肝细胞的Igfbp 2-CreER敲入菌株。在超过1年的稳态期间，2区肝细胞从占据小叶面积的21%-41%大量增加。在用四氯化碳进行中心周围损伤或用3，5-二乙氧羰基-1，4-二氢可力丁（DDC）进行门静脉周围损伤后，IGFBP 2+细胞分别在区3和1中补充损失的肝细胞。IGFBP 2+细胞也优先促进70%部分肝切除术后的再生，以及妊娠期间的肝脏生长。由于IGFBP 2标记随着禁食而大幅增加，我们使用单核转录组学来探索分区作为营养的函数，揭示了劳动力的分区随着禁食而发生显著变化。这些研究证明了IGFBP 2标记的2区肝细胞对肝脏稳态和再生的贡献。
Although midlobular hepatocytes in zone 2 are a recently identified cellular source for liver homeostasis and regeneration, these cells have not been exclusively fate mapped. We generated anIgfbp2-CreERknockin strain that specifically labels midlobular hepatocytes. During homeostasis over 1 year, zone 2 hepatocytes increased in abundance from occupying 21%–41% of the lobular area. After either pericentral injury with carbon tetrachloride or periportal injury with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), IGFBP2+ cells replenished lost hepatocytes in zones 3 and 1, respectively. IGFBP2+ cells also preferentially contributed to regeneration after 70% partial hepatectomy, as well as liver growth during pregnancy. Because IGFBP2 labeling increased substantially with fasting, we used single nuclear transcriptomics to explore zonation as a function of nutrition, revealing that the zonal division of labor shifts dramatically with fasting. These studies demonstrate the contribution of IGFBP2-labeled zone 2 hepatocytes to liver homeostasis and regeneration.