首页|Temporal Integrative Omics Reveals an Increase in Nondegradative Ubiquitylation during Primary Hepatocyte Dedifferentiation

Temporal Integrative Omics Reveals an Increase in Nondegradative Ubiquitylation during Primary Hepatocyte Dedifferentiation

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Primary hepatocytes(PHCs)are widely used in various fields,but the progressive deterioration of liver-specific features in vitro significantly limits their application.While the transcriptional regulation and whole cell proteome(WCP)of PHCs have been extensively studied,only a small number of studies have addressed the role of posttranslational modifications in this process.To elucidate the underlying mecha-nisms that induce dedifferentiation,we carried out parallel quantifications of the transcriptome,WCP,ubiquitinome,and phosphoproteome of rat PHCs after 0,6,12,24,and 48 h of in vitro culture.Our data constitute a detailed proteomic analysis of dedifferentiated PHCs including 2196 proteins,2056 ubiqui-tinated sites,and 4932 phosphorylated peptides.We revealed a low correlation between the transcrip-tome and WCP during dedifferentiation.A combined analysis of the ubiquitinome with the corresponding WCP indicated that the dedifferentiation of PHCs led to an increase in nondegradative K27 ubiquitination.Functional analysis of the altered phosphoproteins suggested a significant enrich-ment in ferroptosis.In all,404 proteins with both ubiquitination and phosphorylation were identified to be involved in critical metabolic events.Furthermore,Ptbpl,Hnrpd,Hnrnpu,and Srrm2 were identified as hub genes.Taken together,our data provide new insights into proteome dynamics during PHC dedif-ferentiation and potential targets to inhibit the dedifferentiation process.

UbiquitinationPhosphoproteomeProteomeDedifferentiationPrimary hepatocytes

Zhengyi Jiang、Zeyu Sun、Xiaoxi Ouyang、Yalei Zhao、Menghao Zhou、Baohong Wang、Qirui Li、Linxiao Fan、Sainan Zhang、Lanjuan Li

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State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,National Clinical Research Center for Infectious Diseases,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,The First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou 310003,China

This work was supported by the National Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of Chinaand Research Unit of Infectious Diseases and Microe-cology,Chinese Academy of Medical Sciences

2016YFC1101304/38140058981790630817906332019RU021

2020

工程(英文)

工程(英文)

CSTPCDSCIEI
ISSN：2095-8099
年,卷(期)：2020.6(11)
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