SoxB1-Mediated Chromatin Remodeling Promotes Sensory Neuron Differentiation in Planarians.

Understanding how adult stem cells generate neurons is critical for advancing regenerative medicine. However, few in vivo models enable studying how stem cell fates are specified as neurons in an adult body. The planarian provides a powerful system for investigating these mechanisms, owing to its abundant adult pluripotent stem cells, termed neoblasts, and its capacity to regenerate a molecularly complex nervous system. The SoxB1 family of transcription factors is broadly implicated in ectodermal lineage commitment. In planarians, the SoxB1 homolog has been shown to promote neural and epidermal differentiation. However, the mechanisms by which influences chromatin dynamics and transcriptional programs during adult neurogenesis remain unknown. To address this, we performed ATAC-seq and RNA-seq on neural-rich head tissues to assess how RNAi knockdown alters chromatin accessibility and gene expression. Disrupting resulted in reduced chromatin accessibility and transcriptional downregulation at neural and epidermal loci, consistent with a pioneer-like role in chromatin priming. We identified 31 candidate downstream targets with concordant accessibility and expression changes, including the transcription factors and , which regulate mechanosensory and ion transport genes. Head tissue sampling enabled the detection of -responsive genes within rare neural subtypes that were missed in our previous whole-body RNA-seq experiments. These findings offer mechanistic insight into adult ectodermal lineage specification and establish a framework for understanding chromatin-mediated neurogenesis in regenerative systems.