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The Spatial Transcriptomic Landscape of the Healing Mouse Intestine Following Damage

Abstract

The intestinal barrier is composed of a complex cell network defining highly compartmentalized and specialized structures. Here, we use spatial transcriptomics to define how the transcriptomic landscape is spatially organized in the steady state and healing murine colon. At steady state conditions, we demonstrate a previously unappreciated molecular regionalization of the colon, which dramatically changes during mucosal healing. Here, we identified spatially-organized transcriptional programs defining compartmentalized mucosal healing, and regions with dominant wired pathways. Furthermore, we showed that decreased p53 activation defined areas with increased presence of proliferating epithelial stem cells. Finally, we mapped transcriptomics modules associated with human diseases demonstrating the translational potential of our dataset. Overall, we provide a publicly available resource defining principles of transcriptomic regionalization of the colon during mucosal healing and a framework to develop and progress further hypotheses.

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References
1.
Baumgartner W . Possible roles of LI-Cadherin in the formation and maintenance of the intestinal epithelial barrier. Tissue Barriers. 2014; 1(1):e23815. PMC: 3879124. DOI: 10.4161/tisb.23815. View

2.
Reinicke A, Laban K, Sachs M, Kraus V, Walden M, Damme M . Ubiquitin C-terminal hydrolase L1 (UCH-L1) loss causes neurodegeneration by altering protein turnover in the first postnatal weeks. Proc Natl Acad Sci U S A. 2019; 116(16):7963-7972. PMC: 6475369. DOI: 10.1073/pnas.1812413116. View

3.
Lin X, Boutros P . Optimization and expansion of non-negative matrix factorization. BMC Bioinformatics. 2020; 21(1):7. PMC: 6945623. DOI: 10.1186/s12859-019-3312-5. View

4.
Kechin A, Boyarskikh U, Kel A, Filipenko M . cutPrimers: A New Tool for Accurate Cutting of Primers from Reads of Targeted Next Generation Sequencing. J Comput Biol. 2017; 24(11):1138-1143. DOI: 10.1089/cmb.2017.0096. View

5.
Arias M, Vande Casteele N, Vermeire S, de Buck van Overstraeten A, Billiet T, Baert F . A panel to predict long-term outcome of infliximab therapy for patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2014; 13(3):531-8. DOI: 10.1016/j.cgh.2014.07.055. View