AUTHOR=Yarani Reza , Palasca Oana , Doncheva Nadezhda T. , Anthon Christian , Pilecki Bartosz , Svane Cecilie A. S. , Mirza Aashiq H. , Litman Thomas , Holmskov Uffe , Bang-Berthelsen Claus H. , Vilien Mogens , Jensen Lars J. , Gorodkin Jan , Pociot Flemming 

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

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=9

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.1081176

DOI=10.3389/fmolb.2022.1081176

ISSN=2296-889X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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 <italic>SPI1, FPR2, TYROBP, CKAP4, MCEMP1, ADGRG3, SLC11A1,</italic> and <italic>SELPLG,</italic> were identified through network centrality ranking and validated in independent human and mouse cohorts.</p><p><bold>Conclusion:</bold> The identified Ulcerative colitis conserved transcriptional signatures aid in the disease phenotyping and future treatment decisions, drug discovery, and clinical trial design.</p>