The spatial transcriptomic landscape of the healing mouse intestine following damage

Sara M. Parigi, Ludvig Larsson, Srustidhar Das, Ricardo O. Ramirez Flores, Annika Frede, Kumar P. Tripathi, Oscar E. Diaz, Katja Selin, Rodrigo A. Morales, Xinxin Luo, Gustavo Monasterio, Camilla Engblom, Nicola Gagliani, Julio Saez-Rodriguez, Joakim Lundeberg and Eduardo J. Villablanca ()
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Sara M. Parigi: Karolinska Institute and University Hospital
Ludvig Larsson: Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology
Srustidhar Das: Karolinska Institute and University Hospital
Ricardo O. Ramirez Flores: Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant
Annika Frede: Karolinska Institute and University Hospital
Kumar P. Tripathi: Karolinska Institute and University Hospital
Oscar E. Diaz: Karolinska Institute and University Hospital
Katja Selin: Karolinska Institute and University Hospital
Rodrigo A. Morales: Karolinska Institute and University Hospital
Xinxin Luo: Karolinska Institute and University Hospital
Gustavo Monasterio: Karolinska Institute and University Hospital
Camilla Engblom: Department of Cell and Molecular Biology, Karolinska Institute
Nicola Gagliani: Karolinska Institute and University Hospital
Julio Saez-Rodriguez: Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant
Joakim Lundeberg: Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology
Eduardo J. Villablanca: Karolinska Institute and University Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28497-0

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