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

Single-cell transcriptomics has significantly advanced regenerative biology by providing detailed insights into cellular and molecular pathways involved in tissue repair across various animal models. This technology has uncovered extensive cell heterogeneity, lineage-biased progenitor subclusters, dedifferentiation processes, and crucial immune interactions that were previously undetectable with bulk estimates. Studies on zebrafish, axolotl, planarian, and mammalian tissues highlight both conserved and species-specific mechanisms involving stem-cell plasticity and key signaling pathways like Wnt, Fgf, Notch, and Tgf-beta. Despite challenges such as dissociation artifacts and loss of spatial context, recent methodological advancements have improved lineage reconstruction and identification of rare regenerative cell states. This review discusses the strengths and weaknesses of current methodologies and emphasizes the potential of integrating multi-omics, spatial mapping, and cross-species comparisons to enhance regenerative medicine applications.