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

被引：42

作者：

Gomez-Salinero, Jesus Maria ^{[1
]}

Izzo, Franco ^{[2
,3
,4
,5
]}

Lin, Yang ^{[1
]}

Houghton, Sean ^{[1
]}

Itkin, Tomer ^{[1
]}

Geng, Fuqiang ^{[1
]}

Bram, Yaron ^{[6
]}

Adelson, Robert P. ^{[7
]}

Lu, Tyler M. ^{[1
,8
]}

Inghirami, Giorgio ^{[9
]}

Xiang, Jenny Zhaoying ^{[10
]}

Lis, Raphael ^{[1
,8
]}

Redmond, David ^{[1
]}

Schreiner, Ryan ^{[1
]}

Rabbany, Sina Y. ^{[1
,7
]}

Landau, Dan A. ^{[2
,3
,4
,5
]}

Schwartz, Robert E. ^{[6
]}

Rafii, Shahin ^{[1
]}

机构：

[1] Weill Cornell Med, Ansary Stem Cell Inst, Hartman Inst Therapeut Organ Regenerat, Dept Med,Div Regenerat Med, New York, NY 10021 USA

[2] Weill Cornell Med, Dept Med, Div Hematol & Med Oncol, New York, NY USA

[3] Weill Cornell Med, Meyer Canc Ctr, New York, NY USA

[4] New York Genome Ctr, New York, NY USA

[5] Weill Cornell Med, Inst Computat Biomed, New York, NY USA

[6] Weill Cornell Med, Dept Med, Div Gastroenterol & Hepatol, New York, NY 10021 USA

[7] Hofstra Univ, Fred DeMatteis Sch Engn & Appl Sci, Bioengn Program, Hempstead, NY 11550 USA

[8] Weill Cornell Med, Ronald O Perelman & Claudia Cohen Ctr Reprod Med, New York, NY 10065 USA

[9] Weill Cornell Med, Dept Pathol & Lab Med, New York, NY USA

[10] Weill Cornell Med, Genom Resources Core Facil, New York, NY USA

来源：

CELL STEM CELL | 2022年 / 29卷 / 04期

关键词：

Expression; c-Maf flox; flox; Decreased sinusoidal genes; HEMATOPOIETIC STEM; RAT-LIVER; ANGIOCRINE SIGNALS; CELLS; DIFFERENTIATION; EXPRESSION; ACTIVATION; PLAYS; GENE;

D O I：

10.1016/j.stem.2022.03.002

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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 through functional and single-cell RNA-sequencing. The acquisition of sinusoidal endothelial cell identity is initiated during early development and 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 the 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 the strategies for vasculature-driven liver repair.

引用

页码：593 / +

页数：25

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