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 cl...

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Autores principales:	Dilek Colak, Olfat Al-Harazi, Osama M. Mustafa, Fanwei Meng, Abdullah M. Assiri, Dipok K. Dhar, Dieter C. Broering
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ef0f5b08fbc48f38f3d976cbddd334f
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spelling	oai:doaj.org-article:3ef0f5b08fbc48f38f3d976cbddd334f2021-12-02T17:04:37ZRNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL10.1038/s41598-020-61826-12045-2322https://doaj.org/article/3ef0f5b08fbc48f38f3d976cbddd334f2020-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-61826-1https://doaj.org/toc/2045-2322Abstract 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, CCND1, FOXM1, TP53, and RB1), transcription factors (Myc, E2F1, TBX2, FOXM1), DNA replication regulators (CDKN1A, EZH2, RRM2), G1/S-transition regulators (CCNB1, CCND1, RABL6), cytokines and growth factors (CSF2, IL-6, TNF, HGF, VEGF, and EGF), ATM and p53 signaling pathways. The functional pathway, upstream, and network analyses revealed both unique and overlapping molecular mechanisms and pathways for each surgical procedure. Identification of molecular signatures and regenerative signaling pathways for each surgical procedure further our understanding of key regulators of liver regeneration as well as patient populations that are likely to benefit from each procedure.Dilek ColakOlfat Al-HaraziOsama M. MustafaFanwei MengAbdullah M. AssiriDipok K. DharDieter C. BroeringNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dilek Colak Olfat Al-Harazi Osama M. Mustafa Fanwei Meng Abdullah M. Assiri Dipok K. Dhar Dieter C. Broering RNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL
description	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, CCND1, FOXM1, TP53, and RB1), transcription factors (Myc, E2F1, TBX2, FOXM1), DNA replication regulators (CDKN1A, EZH2, RRM2), G1/S-transition regulators (CCNB1, CCND1, RABL6), cytokines and growth factors (CSF2, IL-6, TNF, HGF, VEGF, and EGF), ATM and p53 signaling pathways. The functional pathway, upstream, and network analyses revealed both unique and overlapping molecular mechanisms and pathways for each surgical procedure. Identification of molecular signatures and regenerative signaling pathways for each surgical procedure further our understanding of key regulators of liver regeneration as well as patient populations that are likely to benefit from each procedure.
format	article
author	Dilek Colak Olfat Al-Harazi Osama M. Mustafa Fanwei Meng Abdullah M. Assiri Dipok K. Dhar Dieter C. Broering
author_facet	Dilek Colak Olfat Al-Harazi Osama M. Mustafa Fanwei Meng Abdullah M. Assiri Dipok K. Dhar Dieter C. Broering
author_sort	Dilek Colak
title	RNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL
title_short	RNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL
title_full	RNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL
title_fullStr	RNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL
title_full_unstemmed	RNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL
title_sort	rna-seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, allps, and pvl
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/3ef0f5b08fbc48f38f3d976cbddd334f
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RNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL

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