The Promise of Single-Cell RNA Sequencing to Redefine the Understanding of Crohn’s Disease Fibrosis Mechanisms

Author:

Campbell Iona1ORCID,Glinka Michael2ORCID,Shaban Fadlo3,Kirkwood Kathryn J.4,Nadalin Francesca5ORCID,Adams David6,Papatheodorou Irene5ORCID,Burger Albert7,Baldock Richard A.2ORCID,Arends Mark J.2ORCID,Din Shahida1ORCID

Affiliation:

1. Edinburgh Inflammatory Bowel Disease Unit, Western General Hospital, NHS Lothian, Edinburgh EH4 2XU, UK

2. Edinburgh Pathology, Centre for Comparative Pathology, Cancer Research UK Scotland Centre, Institute of Cancer and Genetics, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK

3. Edinburgh Colorectal Unit, Western General Hospital, NHS Lothian, Edinburgh EH4 2XU, UK

4. Department of Pathology, Western General Hospital, NHS Lothian, Edinburgh EH4 2XU, UK

5. European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Hinxton, Cambridge CB10 1SD, UK

6. Experimental Cancer Genetics, Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK

7. Department of Computer Science, School of Mathematical and Computer Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK

Abstract

Crohn’s disease (CD) is a chronic inflammatory bowel disease with a high prevalence throughout the world. The development of Crohn’s-related fibrosis, which leads to strictures in the gastrointestinal tract, presents a particular challenge and is associated with significant morbidity. There are currently no specific anti-fibrotic therapies available, and so treatment is aimed at managing the stricturing complications of fibrosis once it is established. This often requires invasive and repeated endoscopic or surgical intervention. The advent of single-cell sequencing has led to significant advances in our understanding of CD at a cellular level, and this has presented opportunities to develop new therapeutic agents with the aim of preventing or reversing fibrosis. In this paper, we discuss the current understanding of CD fibrosis pathogenesis, summarise current management strategies, and present the promise of single-cell sequencing as a tool for the development of effective anti-fibrotic therapies.

Funder

The Leona M. and Harry B. Helmsley Charitable Trust

The Universities of Edinburgh and Heriot-Watt

NHS Lothian

Welcome Trust Sanger Centre and the European Bioinformatics Unit

Publisher

MDPI AG

Subject

General Medicine

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