Maintenance of multipotency during lengthy periods of cellular quiescence is critical to stem cell function, yet the mechanisms linking multipotency to quiescence remain poorly understood. One candidate for coordinating these processes is the conserved DAF-16/FOXO transcription factor. In response to adverse conditions,
daf-16 promotes entry into the quiescent dauer larva stage midway through larval development. We previously found that during dauer,
daf-16 blocks EGFR/Ras and LIN-12/Notch signaling to promote multipotency in vulval precursor cells. We now show that
daf-16 acts via a distinct mechanism to promote multipotency in hypodermal seam cells during dauer. Larval seam cells are self-renewing and multipotent, whereas adult seam cells are differentiated. MicroRNAs within the heterochronic gene network promote adult seam cell fate. Using RNA-seq and transgenic reporter strains, we find that
daf-16(0) dauer larvae express adult cell fate markers, including
col-19::gfp. Consistent with the aberrant expression of adult cell fate markers,
let-7-family microRNAs are highly and specifically overexpressed in
daf-16(0) dauer larvae. Genetic experiments show that this overexpression contributes to the aberrant
col-19::gfp expression in
daf-16(0) dauers. The LIN-29 transcription factor is the most downstream heterochronic gene and directly activates expression of
col-19 in adults. Surprisingly,
lin-29 is dispensable for the
col-19::gfp phenotype in
daf-16(0) dauer larvae, suggesting that
let-7 family microRNAs act via a novel mechanism to control
col-19::gfp during dauer. As expected given overexpression of
let-7-family microRNAs, RNA-seq data shows that most predicted
let-7-family targets are downregulated in
daf-16(0) dauer larvae. All together, our data suggest a model whereby
daf-16 opposes the transcription of
let-7-family microRNAs, allowing the expression of novel
let-7 target genes that inhibit adult cell fate and maintain multipotency during dauer.