A wound-induced differentiation trajectory for neurons.
Ryan E HulettCarlos Rivera-LópezAndrew R GehrkeAnnika GompersMansi SrivastavaPublished in: Proceedings of the National Academy of Sciences of the United States of America (2024)
Animals capable of whole-body regeneration can replace any missing cell type and regenerate fully functional new organs, including new brains, de novo. The regeneration of a new brain requires the formation of diverse neural cell types and their assembly into an organized structure with correctly wired circuits. Recent work in various regenerative animals has revealed transcriptional programs required for the differentiation of distinct neural subpopulations, however, how these transcriptional programs are initiated in response to injury remains unknown. Here, we focused on the highly regenerative acoel worm, Hofstenia miamia , to study wound-induced transcriptional regulatory events that lead to the production of neurons and subsequently a functional brain. Footprinting analysis using chromatin accessibility data on a chromosome-scale genome assembly revealed that binding sites for the Nuclear Factor Y (NFY) transcription factor complex were significantly bound during regeneration, showing a dynamic increase in binding within one hour upon amputation specifically in tail fragments, which will regenerate a new brain. Strikingly, NFY targets were highly enriched for genes with neuronal function. Single-cell transcriptome analysis combined with functional studies identified soxC + stem cells as a putative progenitor population for multiple neural subtypes. Further, we found that wound-induced soxC expression is likely under direct transcriptional control by NFY, uncovering a mechanism for the initiation of a neural differentiation pathway by early wound-induced binding of a transcriptional regulator.
Keyphrases
- stem cells
- transcription factor
- single cell
- gene expression
- high glucose
- diabetic rats
- dna binding
- nuclear factor
- cell therapy
- drug induced
- white matter
- spinal cord
- public health
- wound healing
- rna seq
- cerebral ischemia
- poor prognosis
- mesenchymal stem cells
- endothelial cells
- toll like receptor
- blood pressure
- electronic health record
- heat shock
- machine learning
- dna damage
- long non coding rna
- surgical site infection
- immune response
- lower limb
- heat shock protein