RNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL

Abstract

The liver is a unique organ that has a phenomenal capacity to regenerate after injury. Different surgical procedures, including partial hepatectomy (PH), intraoperative portal vein ligation (PVL), and associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) show clinically distinct recovery patterns and regeneration. The observable clinical differences likely mirror some underlying variations in the patterns of gene activation and regeneration pathways. In this study, we provided a comprehensive comparative transcriptomic analysis of gene regulation in regenerating rat livers temporally spaced at 24 h and 96 h after PH, PVL, and ALPPS. The time-dependent factors appear to be the most important determinant of post-injury alterations of gene expression in liver regeneration. Gene expression profile after ALPPS showed more similar expression pattern to the PH than the PVL at the early phase of the regeneration. Early transcriptomic changes and predicted upstream regulators that were found in all three procedures included cell cycle associated genes (E2F1,

Identification of Gene Signature as Diagnostic and Prognostic Blood Biomarker for Early Hepatocellular Carcinoma Using Integrated Cross-Species Transcriptomic and Network Analyses

“…The DEGs were mapped to its corresponding gene object in the Ingenuity pathway knowledge base and gene interaction networks. A right-tailed Fisher’s exact test was used to calculate a p -value determining the probability that the biological function (or pathway) assigned to the data set is explained by chance alone ( Colak et al, 2020 ).…”

Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver

“…For instance, RELA, E2F1, GABPB1, ETS2 regulons were active in hepatocytes from P14 and the initiation-progression stage of regeneration, but were turned off in adult hepatocytes and at the termination-rematuration stages (Figure 4C cluster I, 4D), This indicates that these regulons likely play dual roles in regulating the hepatocyte hyperplastic response -i.e., in normal liver development and following an injury in adult animals. In line with our results, previous studies have found that a rapid increase in the expression and/or DNA binding activity of NF-kB (RELA and RELB), E2Fs (E2F1, 3, 4, 6 and 8), AP-1 (JUN and FOS), POLE4, TRP53, MYC, CREM, and ETS (ETS2, GABPB1) family of transcription factors is involved in the initiation of stress signaling, oxidative stress, DNA replication/repair, and cellcycle entry at the early stages of liver regeneration (Baena et al, 2005;Beyer et al, 2008;Bhat et al, 1987;Chaisson et al, 2002;Colak et al, 2020;Iimuro et al, 1998;Inoue et al, 2002a;Kelley-Loughnane et al, 2002;Kurinna et al, 2013;Servillo et al, 1998;Sladky et al, 2020;Stepniak et al, 2006;Su et al, 2002;Westwick et al, 1995;Wu et al, 2013;Yang et al, 1991;Zellmer et al, 2010).…”

Astragaloside IV Suppresses Hepatic Proliferation in Regenerating Rat Liver after 70% Partial Hepatectomy via Down-Regulation of Cell Cycle Pathway and DNA Replication

“…TRIzol ® reagent (Invitrogen, Carlsbad, CA, USA) was used for isolation of total RNA from liver tissue [ 59 ]. cDNA libraries were generated and purified using QuantSeq 3′ mRNA-Seq Library Prep Kit for Illumina (LEXOGEN, Vienna, Austria) according to manufacturer’s instructions.…”