Single-cell analysis uncovers convergence of cell identities during axolotl limb regeneration

TLDR

Axolotl limbs regenerate by rebuilding the skeleton after amputation, but it has been unclear whether preexisting stem cells or dedifferentiation of fibroblasts form the blastema. The authors used transgenic reporter animals to compare contributions of periskeletal cells and fibroblasts during regeneration. Callus‑forming periskeletal cells extended existing bone while fibroblasts constructed new limb segments, and single‑cell transcriptomics and lineage tracing showed that fibroblasts, not preexisting stem cells, dedifferentiate into multipotent skeletal progenitors expressing an embryonic limb program. Gerber et al., Science, this issue p.

Abstract

How the axolotl makes a new limb Unlike most vertebrate limbs, the axolotl limb regenerates the skeleton after amputation. Dermal and interstitial fibroblasts have been thought to provide sources for skeletal regeneration, but it has been unclear whether preexisting stem cells or dedifferentiation of fibroblasts formed the blastema. Gerber et al. developed transgenic reporter animals to compare periskeletal cell and fibroblast contributions to regeneration. Callus-forming periskeletal cells extended existing bone, but fibroblasts built new limb segments. Single-cell transcriptomics and Brainbow-based lineage tracing revealed the lack of a preexisting stem cell. Instead, the heterogeneous population of fibroblasts lost their adult features to form a multipotent skeletal progenitor expressing the embryonic limb program. Science , this issue p. eaaq0681