SoxB1-Mediated Chromatin Remodeling Promotes Sensory Neuron Differentiation in Planarians

Abstract

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 Schmidtea mediterranea 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 soxB1-2 has been shown to promote neural and epidermal differentiation. However, the mechanisms by which soxB1-2 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 soxB1-2 RNAi knockdown alters chromatin accessibility and gene expression. Disrupting soxB1-2 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 castor and mecom, which regulate mechanosensory and ion transport genes. Head tissue sampling enabled the detection of soxB1-2-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.