scAgeCom: a murine atlas of age-related changes in intercellular communication inferred with the package scDiffCom

Abstract

Dysregulation of intercellular communication is a well-established hallmark of aging. To better understand how this process contributes to the aging phenotype, we built scAgeCom, a comprehensive atlas presenting how cell-type to cell-type interactions vary with age in 23 mouse tissues. We first created an R package, scDiffCom, designed to perform differential intercellular communication analysis between two conditions of interest in any mouse or human single-cell RNA-seq dataset. The package relies on its own list of curated ligand-receptor interactions compiled from seven established studies. We applied this tool to single-cell transcriptomics data from the Tabula Muris Senis consortium and the Calico murine aging cell atlas. All the results can be accessed online, using a user-friendly, interactive web application (https://scagecom.org). The most widespread changes we observed include upregulation of immune system processes, inflammation and lipid metabolism, and downregulation of extracellular matrix organization, growth, development and angiogenesis. More specific interpretations are also provided.

Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages

“…However, by analyses of intercellular receptor-ligand interactions in the acute and prolonged autopsy cases we identified several up-and down-regulated signaling pathways, which are probably the outcome of the pro-inflammatory activation [70]. The identified integrin/TGF axis in COVID-19 has been associated with triggering vascular leakage and its blockage could attenuate viral replication in the airway epithelium [71,72].…”

Intercellular communication analysis of the human retinal pigment epithelial and choroidal cells predicts pathways associated with aging, cellular senescence and age-related macular degeneration

“…The study presented herein focused on the communication occurring at the level and between these two tissues, and on the effect that the aging process has on this communication. By applying algorithms that have proved useful to study intercellular communication in various tissues from scRNA-seq data ( Armingol et al, 2021 ; He et al, 2021 ; Hu et al, 2021 ; Jin et al, 2021 ; Lagger et al, 2021 ), we were able to extract important signaling patterns between the RPE and the choroid. Together with our aging and cellular senescence analyses, our analysis predicted three pathways (VEGF, BMP and tenascin) that support some of the strongest RPE/choroid cell–cell interactions, while being significantly affected by age and enhanced between subpopulations of cells showing a senescent-like gene expression profile.…”

“…Intercellular communication (ICC) analysis was performed on the pre-processed Seurat object described above with two R packages relying on different detection methods: CellChat ( Jin et al, 2021 ) and scDiffCom ( Lagger et al, 2021 ). Both algorithms combine the cell type-specific expression of known ligand and receptor genes with permutation tests to assess the biological relevance of potential cell–cell interactions (CCIs).…”

Comparison of methods and resources for cell-cell communication inference from single-cell RNA-Seq data

“…A number of computational tools and resources have emerged that can be further classified as those that predict CCC interactions alone [4][5][6][7][8][9][10][11][12][13][14][15][16][17] , and those that additionally estimate intracellular activities related to CCC [18][19][20][21][22][23][24] . Here, we focus on the former (Table 1).…”