Transient activation of potent progenitor cells is required for spinal cord regeneration

Transient sox2 upregulation and expansion of sox2+ progenitors are thought to underlie their regenerative capacity. Here, we determined the molecular identities, stem cell properties, and contributions of sox2+ progenitors during spinal cord repair.

Genetic lineage tracing shows zebrafish spinal progenitors, while quiescent in uninjured tissues, self-renew and differentiate into neurons and glia after injury. By single-cell sequencing, sox2+ cells are heterogeneous and biased towards neuronal or glial fates in naïve and regenerating tissues. By screening for transcription factors that are differentially expressed in acute versus chronic SCI, we find the BTB domain and CNC homology 1 (Bach1) transcription factors control transient progenitor cell activation by acting as dual activators and repressors of sox2 expression.