{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338973/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Caenorhabditis elegans"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE338973"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"FOXO/DAF-16 modulates the transcription factor ROR/NHR-23 and inhibits the let-7 microRNA to maintain multipotency during dauer","description":"Animals rapidly reprogram gene expression to adapt development to environmental stress. How gene regulatory programs that drive continuous development are repressed during stress-induced developmental arrest remains poorly understood. In Caenorhabditis elegans, starvation and overcrowding trigger entry into the stress-resistant, quiescent dauer stage. Here, we identify interactions among the conserved transcription factors DAF-16/FOXO and NHR-23/ROR, and the let-7 family of microRNAs as key regulators of the switch from continuous development to dauer. We show that loss of daf-16 during dauer causes elevated let-7 family microRNAs and premature expression of the adult collagen reporter col-19p::GFP. Reducing let-7 family activity suppresses this phenotype, whereas dauer-specific let-7 expression is sufficient to induce col-19p::GFP expression. Mechanistically, DAF-16 inhibits let-7 transcription in part by repressing nhr-23, which encodes a transcriptional activator of the let-7 family and molting-cycle genes. ChIP-seq analysis reveals DAF-16 binding upstream of nhr-23, and daf-16; daf-7 mutant dauers exhibit increased nhr-23 mRNA and NHR-23 protein, supporting a model in which DAF-16 directly represses nhr-23. Integrated ChIP-seq and transcriptomic analyses identify 1,183 genes activated and 681 genes repressed by DAF-16 during dauer. Repressed targets are enriched for pro-growth genes involved in mitotic DNA replication and translational elongation. DAF-16 targets include 59 transcription factors that may mediate broader transcriptional reprogramming during dauer to maintain multipotency and establish quiescence. Together, these findings reveal that DAF-16/FOXO establishes stress-induced developmental arrest by coupling activation of protective pathways with repression of conserved developmental timing, growth, and differentiation programs.","dates":{"publication":"2026/07/17"},"accession":"GSE338973","cross_references":{"GSM":["GSM9885886","GSM9885885","GSM9885888","GSM9885887","GSM9885901","GSM9885889","GSM9885900","GSM9885903","GSM9885902","GSM9885880","GSM9885882","GSM9885881","GSM9885884","GSM9885883","GSM9885905","GSM9885904","GSM9885907","GSM9885906","GSM9885909","GSM9885908","GSM9885875","GSM9885897","GSM9885896","GSM9885874","GSM9885910","GSM9885899","GSM9885877","GSM9885898","GSM9885876","GSM9885879","GSM9885878","GSM9885911","GSM9885891","GSM9885890","GSM9885893","GSM9885871","GSM9885892","GSM9885870","GSM9885895","GSM9885873","GSM9885872","GSM9885894"],"GPL":["26672"],"GSE":["338973"],"taxon":["Caenorhabditis elegans"],"PMID":["[42538964]"]}}