TY - JOUR

T1 - Cross-species high-resolution transcriptome profiling suggests biomarkers and therapeutic targets for ulcerative colitis

AU - Yarani, Reza

AU - Palasca, Oana

AU - Doncheva, Nadezhda T.

AU - Anthon, Christian

AU - Pilecki, Bartosz

AU - Svane, Cecilie A.S.

AU - Mirza, Aashiq H.

AU - Litman, Thomas

AU - Holmskov, Uffe

AU - Bang-Berthelsen, Claus H.

AU - Vilien, Mogens

AU - Jensen, Lars J.

AU - Gorodkin, Jan

AU - Pociot, Flemming

N1 - Publisher Copyright: Copyright © 2023 Yarani, Palasca, Doncheva, Anthon, Pilecki, Svane, Mirza, Litman, Holmskov, Bang-Berthelsen, Vilien, Jensen, Gorodkin and Pociot.

PY - 2023

Y1 - 2023

N2 - Background: Ulcerative colitis (UC) is a disorder with unknown etiology, and animal models play an essential role in studying its molecular pathophysiology. Here, we aim to identify common conserved pathological UC-related gene expression signatures between humans and mice that can be used as treatment targets and/or biomarker candidates. Methods: To identify differentially regulated protein-coding genes and non-coding RNAs, we sequenced total RNA from the colon and blood of the most widely used dextran sodium sulfate Ulcerative colitis mouse. By combining this with public human Ulcerative colitis data, we investigated conserved gene expression signatures and pathways/biological processes through which these genes may contribute to disease development/progression. Results: Cross-species integration of human and mouse Ulcerative colitis data resulted in the identification of 1442 genes that were significantly differentially regulated in the same direction in the colon and 157 in blood. Of these, 51 genes showed consistent differential regulation in the colon and blood. Less known genes with importance in disease pathogenesis, including SPI1, FPR2, TYROBP, CKAP4, MCEMP1, ADGRG3, SLC11A1, and SELPLG, were identified through network centrality ranking and validated in independent human and mouse cohorts. Conclusion: The identified Ulcerative colitis conserved transcriptional signatures aid in the disease phenotyping and future treatment decisions, drug discovery, and clinical trial design.

AB - Background: Ulcerative colitis (UC) is a disorder with unknown etiology, and animal models play an essential role in studying its molecular pathophysiology. Here, we aim to identify common conserved pathological UC-related gene expression signatures between humans and mice that can be used as treatment targets and/or biomarker candidates. Methods: To identify differentially regulated protein-coding genes and non-coding RNAs, we sequenced total RNA from the colon and blood of the most widely used dextran sodium sulfate Ulcerative colitis mouse. By combining this with public human Ulcerative colitis data, we investigated conserved gene expression signatures and pathways/biological processes through which these genes may contribute to disease development/progression. Results: Cross-species integration of human and mouse Ulcerative colitis data resulted in the identification of 1442 genes that were significantly differentially regulated in the same direction in the colon and 157 in blood. Of these, 51 genes showed consistent differential regulation in the colon and blood. Less known genes with importance in disease pathogenesis, including SPI1, FPR2, TYROBP, CKAP4, MCEMP1, ADGRG3, SLC11A1, and SELPLG, were identified through network centrality ranking and validated in independent human and mouse cohorts. Conclusion: The identified Ulcerative colitis conserved transcriptional signatures aid in the disease phenotyping and future treatment decisions, drug discovery, and clinical trial design.

KW - biomarkers

KW - coding RNAs

KW - conserved expression signature

KW - non-coding RNAs

KW - ulcerative colitis

U2 - 10.3389/fmolb.2022.1081176

DO - 10.3389/fmolb.2022.1081176

M3 - Journal article

C2 - 36685283

AN - SCOPUS:85146521317

VL - 9

JO - Frontiers in Molecular Biosciences

JF - Frontiers in Molecular Biosciences

SN - 2296-889X

M1 - 1081176

ER -