Ypel5 regulates liver development and function in zebrafish  

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

机构地区：[1]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 200025,China [2]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 [3]Department of Hematology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310011,China [4]Universitéde Paris 7/INSERM/CNRS UMR 944/7212,Equipe Labellisée Ligue Nationale Contre le Cancer,Hôpital St.Louis,Paris 75010,France

出　　处：《Journal of Molecular Cell Biology》2023年第3期44-54,共11页分子细胞生物学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(31371479).

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 mediator that is positively regulated by Ypel5.Zebrafish hnf4a overexpression could largely rescue ypel5 deficiencyinduced hepatic defects.Furthermore,PPARαsignaling 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.

关 键 词：YPEL5 HEPATOMEGALY hepatic function HNF4A PPARαsignaling 

分 类 号：Q78[生物学—分子生物学]