Dataset Information

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.

SUBMITTER: Parigi SM

PROVIDER: S-EPMC8837647 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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The spatial transcriptomic landscape of the healing mouse intestine following damage.

Parigi Sara M SM Larsson Ludvig L Das Srustidhar S Ramirez Flores Ricardo O RO Frede Annika A Tripathi Kumar P KP Diaz Oscar E OE Selin Katja K Morales Rodrigo A RA Luo Xinxin X Monasterio Gustavo G Engblom Camilla C Gagliani Nicola N Saez-Rodriguez Julio J Lundeberg Joakim J Villablanca Eduardo J EJ

Nature communications 20220211 1

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 de ...[more]

PMID: 35149721

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Project description:IntroductionAdvanced paternal age of reproduction is an increasing trend, especially in developed countries and areas. This trend results in elevated risks of adverse reproductive outcomes such as reduced fertility rates, increased pregnancy loss, and poor childhood health. Yet, a systematic profiling of aging-associated molecular and cellular alterations in testicular tissue is still missing.ObjectivesWe aimed to dissect aging-associated molecular characteristics in testes of mice.MethodsSingle-cell transcriptomic sequencing and analysis were conducted in testes of young (2 months old) and old mice (24 months old). Immunofluorescences and immunochemistry were used to characterize aging-associated phenotypes and verify single cell sequence results.ResultsHere, we constructed the first single-cell transcriptomic atlases of testes of young and old mice. In-depth dissection of aging-dependent transcriptional alterations in specific cell types revealed multiple dysregulated biological processes such as increased 'senescence-associated secretory phenotype' and 'inflammation', which were major aging-associated characteristics. Further analysis of aging-related differentially expressed genes uncovered a disrupted balance of undifferentiated and differentiated spermatogonia stem cells in spermatogonia, indicative of a potential role of spermatogonia stem cells in aging-associated subfertility. Importantly, for the first time, our results identified an increased subtype of aging-specific macrophages, which may contribute to a hostile proinflammatory microenvironment during testicular aging.ConclusionTaken together, our findings depict the distinct single-cell transcriptional features of the aged mouse testes and provide enormous resources for a comprehensive understanding of the cell-type-specific molecular mechanisms underlying mouse testicular aging, which may shed light on developing novel potential diagnostic biomarkers and therapeutic targets for age-associated male subfertility.

Dataset Information

The spatial transcriptomic landscape of the healing mouse intestine following damage.

Publications

The spatial transcriptomic landscape of the healing mouse intestine following damage.

Similar Datasets

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