A blastema in sea star larvae integrates wound signaling to drive regeneration-specific and developmental gene expression patterns
Year: 2026
Type: preprint
Abstract: Whether regeneration depends on the reactivation of developmental programs, regeneration-specific regulatory mechanisms, or both remains a central question in regeneration biology. Here, we investigate these processes in regenerating larvae of the sea star Patiria miniata, a deuterostome with robust regenerative capacity. By integrating single-nucleus transcriptomics with chromatin accessibility profiling across development and regeneration, we identify a regeneration-induced blastema cell state that is molecularly distinct from pre-existing larval populations and serves as the source of regenerated tissues. We show that regeneration is associated with distinct classes of regeneration-responsive enhancers, including regeneration-specific elements and enhancers reused from development, which link wounding signals to gene regulatory network (GRN) activation. These enhancer classes converge on regulatory programs associated with the transcription factor Runx, positioning Runx as a central node within the inferred regeneration GRN. Notably, we identify a Runx-associated regulatory framework that provides a mechanistic explanation for the de novo emergence of sox4⁺ cells during regeneration through novel deployment of developmentally shared enhancers. Together, our results provide a framework for how wound-induced signals specify regenerative cell states and how regeneration-specific and developmental gene regulatory networks may be coordinated to rebuild lost tissues. Teaser Distinct enhancer classes link injury signals to developmental gene networks during regeneration
Institutions: Carnegie Mellon University, Marian University - Indiana, University of Maryland, Baltimore, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Wexner Medical Center, The Ohio State University, University of Florida
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7214004608