GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325618/primaryOK200TranscriptomicsCaenorhabditis elegansExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325618GEOGSEfalseDepletion of Canonical Histones Enhances Direct Reprogramming of Scavenger Cells in vivoDirect reprogramming is a procedure that converts the identity of differentiated cells, which can be triggered by defined transcription factors (TFs). Cellular reprogramming offers a promising approach for replacing damaged cells and repairing diseased tissues. In this context, understanding the implications of diverse molecular pathways that regulate cell fate conversion in vivo is necessary to ensure the safety and efficacy of reprogrammed cell therapy. The nematode C. elegans is a powerful model organism for dissecting molecular processes in vivo and has previously been used to identify reprogramming barriers that are conserved in mammals. Here, we describe the discovery of an unprecedented TF-induced direct reprogramming instance that allows the conversion of mesodermal scavenger cells with hepatic function, known as coelomocytes (CCs) in C. elegans. Direct reprogramming of CCs into neuron-like cells results in the acquisition of neuronal characteristics with corresponding gene expression. Moreover, CCs can also be directly reprogrammed into intestinal cells. This conversion is accompanied by striking morphological changes, including the formation of a single-cell lumen and the development of microvilli, which underlines the acquisition of an intestinal cell fate. Using reverse genetics by RNAi, we demonstrate that direct reprogramming of CCs can be enhanced upon depletion of specific chromatin-related factors. Notably, knocking down canonical histones substantially enhanced reprogramming. Reducing histone levels is expected to affect chromatin states and gene expression, while improved cell fate conversion upon histone depletion has not been previously reported.2026/03/26GSE325618GSM9609623GSM9609624GSM9609625GSM9609620GSM9609621GSM960962219757325618Caenorhabditis elegans