Single-Cell Transcriptomics to Map Cellular Heterogeneity in Tissue Regeneration Models

Abstract

Single-cell transcriptomics has also revolutionized regenerative biology by offering a resolution never before achieved into both the cellular and molecular pathways mediating tissue repair in different animal models. Through profiling of thousands of individual cells throughout the regenerative process, this technology has revealed widespread cell heterogeneity, lineage-biased progenitor subclusters, active dedifferentiation processes, and pivotal immune interactions between niche that have been lost by bulk estimates. Zebrafish, axolotl, planarian, and mammalian tissue studies demonstrating conservation and species-specificity of stem-cell plasticity, immune modulation and main signaling pathways, Wnt, Fgf, Notch and Tgf- beta, provide insights into conserved and species-specific mechanisms of these developmental changes. Recent methodological progress such as optimised dissociation-based assays, single-nucleus RNA sequencing and the ability to compute lineage relations and find uncommon regenerative cell states have facilitated the reconstitution of lineages and the recovery of rare regenerative cell states. In spite of issues associated with dissociation artifacts, the loss of spatial context, and the variation between studies, the single-cell technologies still transform the knowledge of the regeneration and promise a lucrative translational outlook on generating regenerative therapies that are more specific. This is a review that compiles the recent evidence, analyzes the methodology strengths and weaknesses, and reports the future prospects in bringing together multi-omics, spatial mapping, lineage tracing and cross-species comparisons to complement the mechanistic aspect and hastens the applications of regenerative medicine.