scDiffCom: a tool for differential analysis of cell–cell interactions provides a mouse atlas of aging changes in intercellular communication

Cyril Lagger, Eugen Ursu, Anaïs Equey, Roberto A. Avelar, Angela Oliveira Pisco, Robi Tacutu, João Pedro de Magalhães*

*Corresponding author for this work

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Abstract

Dysregulation of intercellular communication is a hallmark of aging. To better quantify and explore changes in intercellular communication, we present scDiffCom and scAgeCom. scDiffCom is an R package, relying on approximately 5,000 curated ligand–receptor interactions, that performs differential intercellular communication analysis between two conditions from single-cell transcriptomics data. Built upon scDiffCom, scAgeCom is an atlas of age-related cell–cell communication changes covering 23 mouse tissues from 58 single-cell RNA sequencing datasets from Tabula Muris Senis and the Calico murine aging cell atlas. It offers a comprehensive resource of tissue-specific and sex-specific aging dysregulations and highlights age-related intercellular communication changes widespread across the whole body, such as the upregulation of immune system processes and inflammation, the downregulation of developmental processes, angiogenesis and extracellular matrix organization and the deregulation of lipid metabolism. Our analysis emphasizes the relevance of the specific ligands, receptors and cell types regulating these processes. The atlas is available online (https://scagecom.org).
Original languageEnglish
Pages (from-to)1446-1461
Number of pages16
JournalNature Aging
Volume3
Issue number11
Early online date2 Nov 2023
DOIs
Publication statusPublished - Nov 2023

Bibliographical note

Acknowledgements
We thank J. Kimmel for helpful information regarding the Calico murine cell atlas, K. Tsuyuzaki for general discussion regarding intercellular communication at the early stage of this project, Z. Abidi for support to deploy the Shiny app and U. Castet for useful suggestions on the manuscript. C.L. is grateful for the funding provided by the Human Frontier Science Program (fellowship LT000741/2019-C). Our work in the Integrative Genomics of Ageing Group was further supported by grants from the Wellcome Trust (208375/Z/17/Z), LongeCity and the Biotechnology and Biological Sciences Research Council (BB/R014949/1) to J.P.d.M. R.T. and E.U. were supported by the National Authority for Scientific Research and Innovation and by the Ministry of European Funds, Romania, through the Competitiveness Operational Program 2014–2020, POC-A.1-A.1.1.4-E-2015 (grant no.: 40/02.09.2016, ID: P_37_778, to R.T.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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