Ypel5 regulates liver development and function in zebrafish

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外文摘要：YPEL5 is a member of the Yippee-like(YPEL)gene family that is evolutionarily conserved in eukaryotic species.To date,the physiological function of YPEL5 has not been assessed due to a paucity of genetic animal models.Here,using CRISPR/Cas9-mediated genome editing,we generated a stable ypel5-/-mutant zebrafish line.Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation.Meanwhile,hepatic metabolism and function are dysregulated in ypel5-/-mutant zebrafish,as revealed by metabolomic and transcriptomic analyses.Mechanistically,Hnf4a is identified as a crucial downstream mediatorthat is positively regulated by Ypel5.Zebrafish hnf4a overexpression could largely rescue ypel5 deficiency-induced hepatic defects.Furthermore,PPARα signaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of the Hnf4a gene.Herein,this work demonstrates an essential role of Ypel5 in hepatocyte proliferation and function and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrates.

外文关键词：

YPEL5hepatomegalyhepatic functionHNF4APPARα signaling

作者：

Yun Deng、Xiao Han、Huiqiao Chen、Chaoxian Zhao、Yi Chen、Jun Zhou、Hugues de The、Jun Zhu、Hao Yuan

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作者单位：

Shanghai Institute of Hematology,State Key Laboratory of Medical Genomics,National Research Center for Translational Medicine at Shanghai,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 20002 5,China

CNRS-LIA Hematology and Cancer,Sino-French Research Center for Life Sciences and Genomics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China

Department of Hematology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310011,China

Université de Paris 7/INSERM/CNRS UMR 944/7212,Equipe Labellisée Ligue Nationale Contre le Cancer,Hôpital St.Louis,Paris 75010,France

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基金：

National Natural Science Foundation of China

项目编号：

31371479

出版年：

2023

DOI：

10.1093/jmcb/mjad019

分子细胞生物学报(英文版)