1. Multi-omics network analysis on samples from sequential biopsies reveals vital role of proliferation arrest for Macrosteatosis related graft failure in rats after liver transplantation.
- Author
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Liu, Zhengtao, Wang, Wenchao, Li, Xiang, Zhao, Junsheng, Zhu, Hai, Que, Shuping, He, Yong, Xu, Jun, Zhou, Lin, Mardinoglu, Adil, and Zheng, Shusen
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LIVER transplantation , *MULTIOMICS , *CHOLINE , *FOCAL adhesions , *GENE regulatory networks , *DNA replication - Abstract
To investigate the molecular impact of graft MaS on post-transplant prognosis, based on multi-omics integrative analysis. Rats were fed by methionine-choline deficient diet (MCD) for MaS grafts. Samples were collected from grafts by sequential biopsies. Transcriptomic and metabolomic profilings were assayed. Post-transplant MaS status showed a close association with graft failure. Differentially expressed genes (DEGs) for in-vivo MaS were mainly enriched on pathways of cell cycle and DNA replication. Post-transplant MaS caused arrests of graft regeneration via inhibiting the E2F1 centered network, which was confirmed by an in vitro experiment. Data from metabolomics assays found insufficient serine/creatine which is located on one‑carbon metabolism was responsible for MaS-related GF. Pre-transplant MaS caused severe fibrosis in long-term survivors. DEGs for grafts from long-term survivors with pre-transplant MaS were mainly enriched in pathways of ECM-receptor interaction and focal adhesion. Transcriptional regulatory network analysis confirmed SOX9 as a key transcription factor (TF) for MaS-related fibrosis. Metabolomic assays found elevation of aromatic amino acid (AAA) was a major feature of fibrosis in long-term survivors. Graft MaS in vivo increased post-transplant GF via negative regulations on graft regeneration. Pre-transplant MaS induced severe fibrosis in long-term survivors via activations on ECM-receptor interaction and AAA metabolism. • MaS in vivo affects postoperative survival status for rats LT receivors; • MaS caused GF via suppressed regeneration E2F1 centered TRN; • Pre-transplant MaS causes fibrosis in long-term survivors via SOX9 centered TRN. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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