Specification of fetal liver endothelial progenitors to functional zonated adult sinusoids requires c-Maf induction.
Specification of fetal liver endothelial progenitors to functional zonated adult sinusoids requires c-Maf induction.
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DOI：
10.1016/j.stem.2022.03.002
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发表时间：
2022-04-07
期刊：
影响因子：
23.9
通讯作者：
Rafii, Shahin
中科院分区：
文献类型：
--
作者：
Gomez-Salinero, Jesus Maria;Izzo, Franco;Lin, Yang;Houghton, Sean;Itkin, Tomer;Geng, Fuqiang;Bram, Yaron;Adelson, Robert P.;Lu, Tyler M.;Inghirami, Giorgio;Xiang, Jenny Zhaoying;Lis, Raphael;Redmond, David;Schreiner, Ryan;Rabbany, Sina Y.;Landau, Dan A.;Schwartz, Robert E.;Rafii, Shahin
肝血管网由窦状隙和肝细胞共带形成。肝内血管如何获得其分级专门功能尚不清楚。我们通过功能和单细胞RNA测序研究小鼠发育过程中肝血管细胞的异质性。窦状隙内皮细胞身份的获得在早期发育期间开始，并在出生后完成，起源于E12时的未分化血管祖细胞库。围产期诱导的转录因子c-Maf是一个关键的开关正弦身份确定。c-Maf的内皮素限制性缺失破坏肝窦发育，异常地扩大出生后肝造血，促进出生后过度的窦增殖，并增加肝促纤维化对化学损伤的敏感性。在普通人内皮细胞中强制c-Maf过表达开启维持肝细胞功能的肝窦转录程序。c-Maf代表肝窦细胞身份的可诱导的器官内型和小生境响应分子决定因素，并为血管驱动的肝脏修复策略奠定基础。血管适应每个器官的需要。在肝脏中，这种适应是从胎儿到出生后发育的渐进过渡，这是由转录因子c-Maf促进的。体外c-Maf诱导肝样血管表型，允许长期肝细胞共培养。
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 through functional and single-cell RNA sequencing. The acquisition of sinusoidal endothelial cell identity is initiated during early development and is completed postnatally, originating from a pool of undifferentiated vascular progenitors at E12. The peri-natal induction of the transcription factor c-Maf is a critical switch for sinusoidal identity determination. Endothelium restricted deletion of c-Maf disrupts liver sinusoidal development, aberrantly expands postnatal liver hematopoiesis, promotes excessive postnatal sinusoidal proliferation, and aggravates liver pro-fibrotic sensitivity to chemical insult. Enforced c-Maf overexpression in generic human endothelial cells switches on a liver sinusoidal transcriptional program that maintains hepatocyte function. c-Maf represents an inducible intra-organotypic and niche responsive molecular determinant of hepatic sinusoidal cell identity and lays the foundation for strategies for vasculature-driven liver repair. Blood vessels adapt to the requirements of each organ. In the liver, this adaptation is a progressive transition from fetal to postnatal development, that is facilitated by the transcription factor c-Maf. In vitro c-Maf induces a liver like vascular phenotype allowing long term hepatocyte co-culture.
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影响因子：
11.8
作者：
Inverso D;Shi J;Lee KH;Jakab M;Ben-Moshe S;Kulkarni SR;Schneider M;Wang G;Komeili M;Vélez PA;Riedel M;Spegg C;Ruppert T;Schaeffer-Reiss C;Helm D;Singh I;Boutros M;Chintharlapalli S;Heikenwalder M;Itzkovitz S;Augustin HG
通讯作者：
Augustin HG
影响因子：
16.6
作者：
Dejana E;Hirschi KK;Simons M
通讯作者：
Simons M
影响因子：
10.5
作者：
Hansen, Amy;Henderson, Stephen;Boshoff, Chris
通讯作者：
Boshoff, Chris
DOI：
10.1016/s0889-1605(86)80018-0
发表时间：
1986-10-01
期刊：
JOURNAL OF ULTRASTRUCTURE AND MOLECULAR STRUCTURE RESEARCH
影响因子：
--
作者：
BARBERAGUILLEM, E;ARRUE, JM;VIDALVANACLOCHA, F
通讯作者：
VIDALVANACLOCHA, F
影响因子：
11.4
作者：
Giordano, Marilyn;Henin, Coralie;Verdeil, Gregory
通讯作者：
Verdeil, Gregory