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Genomic Perspectives on Cell Fate Reprogramming in the Caenorhabditis elegans Germline

Posted on:2015-03-16Degree:Ph.DType:Dissertation
University:The University of Wisconsin - MadisonCandidate:Sorokin, Elena PFull Text:PDF
GTID:1474390017997762Subject:Developmental Biology
Abstract/Summary:
In multicellular organisms, genetic programs guide cells to adopt particular cell fates as tissues are formed during development, maintained in adults and repaired after injury. Cell fates can also be reprogrammed artificially by genetic or chemical manipulation. In Caenorhabditis elegans, germ cell fate can be chemically reprogrammed: mutant puf-8; lip-1 adult hermaphrodites make sperm but can be switched to oocyte production by treatment with a MEK inhibitor. Such chemical reprogramming is uncommon: out of six genetically diverse sperm-only mutant backgrounds, only one other mutant could undergo chemical reprogramming, fbf-1; lip-1. Reprogramming "competence" thus depends on genotype. In addition, we show that two genes encoding PUF family member RNA-binding proteins, puf-8 and fbf-1, are redundantly required for chemical reprogramming of germ cell fate. Next, genomic analysis of reprogramming competent worms revealed an enrichment of oogenic mRNAs relative to mutants lacking the competence for chemical reprogramming. This intermediate state also existed at the protein level, since puf-8; lip-1 and fbf-1; lip-1 mutants expressed proteins diagnostic of both sperm and oocyte. Therefore reprogramming competent mutants possess an intersexual molecular profile at both RNA and protein levels. This intersexual molecular signature may poise the germline tissue for changing its cellular sexual state in response to environmental cues.
Keywords/Search Tags:Cell, Reprogramming
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