TIME-COURSE SWRNA-SEQ UNCOVERS A HIERARCHICAL GENE REGULATORY NETWORK IN CONTROLLING THE RESPONSE-REPAIR-REMODELING AFTER WOUNDING

Time-course swRNA-seq uncovers a hierarchical gene regulatory network in controlling the response-repair-remodeling after wounding

Time-course swRNA-seq uncovers a hierarchical gene regulatory network in controlling the response-repair-remodeling after wounding

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Abstract Wounding initiates intricate responses crucial for tissue repair and regeneration.Yet, the gene regulatory networks governing wound healing remain poorly understood.Here, employing single-worm RNA sequencing (swRNA-seq) across 12 time-points, we delineated a three-stage wound repair process in C.elegans: response, repair, and remodeling.Integrating diverse datasets, we constructed a dynamic regulatory network comprising 241 transcription regulators and their inferred targets.

We identified potentially seven autoregulatory TFs and five cross-autoregulatory chiggate.com loops involving pqm-1 and jun-1.We revealed that TFs might interact with chromatin factors and form TF-TF combinatory modules via intrinsically disordered regions to enhance response robustness.We experimentally validated six regulators functioning in transcriptional and translocation-dependent manners.Notably, nhr-76, 15-eg2373cl daf-16, nhr-84, and oef-1 are potentially required for efficient repair, while elt-2 may act as an inhibitor.These findings elucidate transcriptional responses and hierarchical regulatory networks during C.

elegans wound repair, shedding light on mechanisms underlying tissue repair and regeneration.

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