Transfer learning in a biomaterial fibrosis model identifies in vivo senescence heterogeneity and contributions to vascularization and matrix production across species and diverse pathologies

Cellular senescence promotes progenitor cell expansion during axolotl limb regeneration

“…Although mechanistic links between ribosome biogenesis and senescence induction have been previously established, this represents a relatively under-explored aspect of senescence and its prevalence in other in vivo contexts merits further investigation. In addition, we uncover the heterogeneous subpopulations that comprise the total bSC population (Figure 3J) and find that bSCs consist predominantly of cells of connective tissue and macrophage-origins, with minor contributions from other cell types, consistent with recent reports of retention of cell-type identity following senescence induction 39,40 . As our characterizations relied on nanoparticle-based isolation, there is a possibility that macrophages could be non-specifically labelled due to their phagocytic activity 41 .…”

The foreign body response: emerging cell types and considerations for targeted therapeutics

“…Cherry et al found senescent pericytes and cartilage-like fibroblasts in scRNAseq datasets of mouse and human FBR. 130 Several studies suggest that material-dependent properties play a role in influencing the senescent phenotype in cells. In a study comparing chitosan, polyvinyl alcohol (PVA), and poly (2-hydroxyethyl methacrylate) ( pHEMA), Tsai et al found that only senescent fibroblasts cultured on chitosan had reduced β-gal activity and increased proliferative capacity.…”

“…Additionally, researchers can use computational algorithms on single-cell transcriptomic data to reconstruct intercellular signaling networks and characterize biomaterial-specific responses. 130 These techniques are critical for deepening our understanding of stromal-immune and senescent-immune cell interactions in the FBR. For instance, the computational algorithm described in Cherry et al could probe the signaling network between p16 + senescent cells and Th17 cells in Chung et al 19,130 Therefore, as technologies advance, the field can progress toward studying cells in the context of a network of interactions rather than cells in isolation.…”

Targeting Senescent Cells as Therapy for CKD

“…39,40 Recently developed technologies combining single-cell resolution analysis while retaining their spatial context have the potential to advance the field further with an increasing need for computational tools to maximize the yield, interpretation, and robustness of data from each study performed. 41,42 Senescence-Associated Secretory Phenotype (SASP)…”