小柯机器人

美国威尔康奈尔医学院Shahin Rafii、Jesus Maria Gómez-Salinero等研究人员合作发现，胎儿肝脏内皮细胞祖细胞向功能分区的成体肝窦分化需要c-Maf的诱导。2022年3月31日，国际知名学术期刊《细胞—干细胞》在线发表了这一成果。

研究人员通过功能和单细胞RNA测序来研究了小鼠发育期间肝脏血管细胞的异质性。窦状内皮细胞身份的获得是在早期发育过程中开始的，并在出生后完成，在E12时起源于未分化的血管祖细胞库。转录因子c-Maf的围产期诱导是决定窦状内皮细胞身份的一个关键开关。

对c-Maf的内皮限制性缺失会破坏肝脏窦道的发育，反常地扩大产后肝脏的造血功能，促进产后窦道的过度增殖，并加重肝脏对化学损伤的敏感性。c-Maf在普通人类内皮细胞中的强制过表达会开启维持肝细胞功能的肝窦转录程序。c-Maf代表了肝窦体细胞身份的一种分子决定因素，为血管驱动的肝脏修复策略奠定了基础。

据悉，肝脏的血管网络是由肝窦和肝细胞共区构成的。肝内血管如何获得其专门的功能尚不清楚。

附：英文原文

Title: Specification of fetal liver endothelial progenitors to functional zonated adult sinusoids requires c-Maf induction

Author: Jesus Maria Gómez-Salinero, Franco Izzo, Yang Lin, Sean Houghton, Tomer Itkin, Fuqiang Geng, Yaron Bram, Robert P. Adelson, Tyler M. Lu, Giorgio Inghirami, Jenny Zhaoying Xiang, Raphael Lis, David Redmond, Ryan Schreiner, Sina Y. Rabbany, Dan A. Landau, Robert E. Schwartz, Shahin Rafii

Issue&Volume: 2022-03-31

Abstract: The liver vascular network is patterned by sinusoidal and hepatocyte co-zonation.How intra-liver vessels acquire their hierarchical specialized functions is unknown.We study heterogeneity of hepatic vascular cells during mouse development throughfunctional and single-cell RNA-sequencing. The acquisition of sinusoidal endothelialcell identity is initiated during early development and completed postnatally, originatingfrom a pool of undifferentiated vascular progenitors at E12. The peri-natal inductionof the transcription factor c-Maf is a critical switch for the sinusoidal identitydetermination. Endothelium-restricted deletion of c-Maf disrupts liver sinusoidaldevelopment, aberrantly expands postnatal liver hematopoiesis, promotes excessivepostnatal sinusoidal proliferation, and aggravates liver pro-fibrotic sensitivityto chemical insult. Enforced c-Maf overexpression in generic human endothelial cellsswitches on a liver sinusoidal transcriptional program that maintains hepatocyte function.c-Maf represents an inducible intra-organotypic and niche-responsive molecular determinantof hepatic sinusoidal cell identity and lays the foundation for the strategies forvasculature-driven liver repair.

DOI: 10.1016/j.stem.2022.03.002

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00100-X

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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