title: An in vivo requirement for the mediator subunit med14 in the maintenance of stem cell populations.
abstract: The 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.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors.forename: Jeffrey T A
authors.initials: JT
authors.lastname: Burrows
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors.forename: Bret J
authors.initials: BJ
authors.lastname: Pearson
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Richard Lewar Centre for Excellence in Cardiovascular Research, Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada. Electronic address: ian.scott@sickkids.ca.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Scott
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000235:genetics; D000066673:Cell Self Renewal / Q000235:genetics*; D015870:Gene Expression; D007150:Immunohistochemistry; D056892:Mediator Complex / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: C515835:Med14 protein, zebrafish; D056892:Mediator Complex; D021122:Protein Subunits; D029961:Zebrafish Proteins