Saraswathy, V. | Search bioRxiv

bioRxiv2026

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

Adult zebrafish exhibit full recovery following spinal cord injury. Transient expansion of stem cell-like progenitors is thought to underlie their regenerative capacity. Yet, our understanding of the identities and contributions of the crucial stem cell populations that direct spontaneous neural repair remains limited. Moreover, while most neural regeneration research is centered on promoting proliferative repair, the regulatory mechanisms that reinstate quiescence post-repair are unknown. Here, we determined the molecular identities and cellular 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 both homeostatic and regenerating tissues. By screening for transcription factors that are differentially expressed in acute versus chronic spinal cord injury, we find the Bach1 transcription factors control transient progenitor cell activation by acting as dual activators and repressors of sox2 expression. This study elucidates the molecular diversity and contributions of sox2 expressing cells during spinal cord repair and identifies a transcriptional regulatory switch by which progenitor cells expand after injury and restore quiescence after regeneration is completed.

neuroscience↗

bioRxiv2025

Hb-EGF directs systemic muscle repair

Regenerative capacity varies between tissues, species, and stages of the life cycle. What is less appreciated is that regenerative capacity also varies with the magnitude of the injury, even within a single tissue. Vertebrate skeletal muscle efficiently regenerates following minor injuries; however, extensive injuries may result in incomplete repair, which can be debilitating. To understand if small- and large-scale muscle injuries activate distinct regenerative programs, we developed a systemic muscle injury model in zebrafish. Transcriptomic analysis of muscle and non-muscle tissues revealed that systemic and local muscle injuries elicit distinct molecular responses, both quantitatively and qualitatively. Systemic muscle injury activated the expression of Heparin binding epidermal-like growth factor (Hb-EGF) in the epidermis, and Hb-EGF is necessary for systemic muscle repair. Conversely, local muscle injury did not induce Hb-EGF expression and Hb-EGF was not required for local muscle repair. These studies suggest that large- and small-scale muscle injuries activate different regenerative programs, resulting in either systemic or local repair.

developmental biology↗