An In Vivo Requirement for the Mediator Subunit Med14 in the Maintenance of Stem Cell Populations

•med14 mutant zebrafish embryos do not have global defects in transcription•Mediator components are required in planaria for adult stem cell maintenance•Zebrafish med14 mutant embryos have an apparent defect in stem cell maintenance•Mediator has a specialized in vivo function in stem cell lineages

SummaryThe Mediator complex has recently been shown to be a key player in the maintenance of embryonic and induced pluripotent stem cells. However, the in vivo consequences of loss of many Mediator subunits are unknown. We identified med14 as the gene affected in the zebrafish logelei (log) mutant, which displayed a morphological arrest by 2 days of development. Surprisingly, microarray analysis showed that transcription was not broadly affected in log mutants. Indeed, log cells transplanted into a wild-type environment were able to survive into adulthood. In planarians, RNAi knockdown demonstrated a requirement for med14 and many other Mediator components in adult stem cell maintenance and regeneration. Multiple stem/progenitor cell populations were observed to be reduced or absent in zebrafish med14 mutant embryos. Taken together, our results show a critical, evolutionarily conserved, in vivo function for Med14 (and Mediator) in stem cell maintenance, distinct from a general role in transcription.