TY - JOUR
T1 - Transcriptome profiling of ulcerative colitis mouse model suggests biomarkers and therapeutic targets for human colitis
AU - Yarani, Reza
AU - Palasca, Oana
AU - Doncheva, Nadezhda Tsankova
AU - Anthon, Christian
AU - Pilecki, Bartosz
AU - Svane, Cecilie A. S.
AU - Mirza, Aashiq Hussain
AU - Litman, Thomas
AU - Holmskov, Uffe
AU - Bang-Berthelsen, Claus Heiner
AU - Vilien, Mogens
AU - Jensen, Lars J.
AU - Gorodkin, Jan
AU - Pociot, Flemming
PY - 2020
Y1 - 2020
N2 - BACKGROUND & AIMS Ulcerative colitis (UC) is an inflammatory bowel disorder with unknown etiology. Given its complex nature, in vivo studies to investigate its pathophysiology is vital. Animal models play an important role in molecular profiling necessary to pinpoint mechanisms that contribute to human disease. Thus, we aim to identify common conserved gene expression signatures and differentially regulated pathways between human UC and a mouse model hereof, which can be used to identify UC patients from healthy individuals and to suggest novel treatment targets and biomarker candidates.
METHODS Therefore, we performed high-throughput total and small RNA sequencing to comprehensively characterize the transcriptome landscape of the most widely used UC mouse model, the dextran sodium sulfate (DSS) model. We used this data in conjunction with publicly available human UC transcriptome data to compare gene expression profiles and pathways.
RESULTS We identified differentially regulated protein-coding genes, long non-coding RNAs and microRNAs from colon and blood of UC mice and further characterized the involved pathways and biological processes through which these genes may contribute to disease development and progression. By integrating human and mouse UC datasets, we suggest a set of 51 differentially regulated genes in UC colon and blood that may improve molecular phenotyping, aid in treatment decisions, drug discovery and the design of clinical trials.
CONCLUSION Global transcriptome analysis of the DSS-UC mouse model supports its use as an efficient high-throughput tool to discover new targets for therapeutic and diagnostic applications in human UC through identifying relationships between gene expression and disease phenotype.
AB - BACKGROUND & AIMS Ulcerative colitis (UC) is an inflammatory bowel disorder with unknown etiology. Given its complex nature, in vivo studies to investigate its pathophysiology is vital. Animal models play an important role in molecular profiling necessary to pinpoint mechanisms that contribute to human disease. Thus, we aim to identify common conserved gene expression signatures and differentially regulated pathways between human UC and a mouse model hereof, which can be used to identify UC patients from healthy individuals and to suggest novel treatment targets and biomarker candidates.
METHODS Therefore, we performed high-throughput total and small RNA sequencing to comprehensively characterize the transcriptome landscape of the most widely used UC mouse model, the dextran sodium sulfate (DSS) model. We used this data in conjunction with publicly available human UC transcriptome data to compare gene expression profiles and pathways.
RESULTS We identified differentially regulated protein-coding genes, long non-coding RNAs and microRNAs from colon and blood of UC mice and further characterized the involved pathways and biological processes through which these genes may contribute to disease development and progression. By integrating human and mouse UC datasets, we suggest a set of 51 differentially regulated genes in UC colon and blood that may improve molecular phenotyping, aid in treatment decisions, drug discovery and the design of clinical trials.
CONCLUSION Global transcriptome analysis of the DSS-UC mouse model supports its use as an efficient high-throughput tool to discover new targets for therapeutic and diagnostic applications in human UC through identifying relationships between gene expression and disease phenotype.
KW - DSS
KW - UC
KW - Transcriptomics
KW - Colon
KW - Blood
U2 - 10.1101/2020.08.12.225458
DO - 10.1101/2020.08.12.225458
M3 - Journal article
JO - bioRxiv
JF - bioRxiv
ER -