Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Comparison of Zfp706GT and ZfpGT REV ES cells in 2i


ABSTRACT: Self-renewal circuitry in embryonic stem (ES) cells is increasingly defined. How the robust pluripotency programme is dissolved to enable fate transition is less appreciated. We developed a forward genetic approach using haploid ES cells. We created libraries of transposon integrations and screened for persistent self-renewal in differentiation permissive culture. This yielded multiple mutants in the FGF/Erk and GSK3/Tcf3 modules known to drive differentiation, and in epigenetic modifiers implicated in lineage commitment. We also identified and validated factors not previously considered. These include the conserved small zinc finger protein Zfp706. Loss of Zfp706 function severely delays the exit from self-renewal. To asses a potential function of Zfp706 in regulation of gene expression we compared transcription profiles between Zfp706 gene trap mutant ES cells and genetic revertants. Assessment of differentially expressed genes in Zfp706 gene trap mutants obtained in a haploid ES cell screen for effectors of ES cell differentiation vs. genetic revertants generated by Flp-e mediated excision of the gene trap cassette

ORGANISM(S): Mus musculus

SUBMITTER: Martin Leeb 

PROVIDER: E-GEOD-53194 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genetic exploration of the exit from self-renewal using haploid embryonic stem cells.

Leeb Martin M   Dietmann Sabine S   Paramor Maike M   Niwa Hitoshi H   Smith Austin A  

Cell stem cell 20140109 3


Self-renewal circuitry in embryonic stem cells (ESCs) is increasingly defined. How the robust pluripotency program is dissolved to enable fate transition is less appreciated. Here we develop a forward genetic approach using haploid ESCs. We created libraries of transposon integrations and screened for persistent self-renewal in differentiation-permissive culture. This yielded multiple mutants in the Fgf/Erk and GSK3/Tcf3 modules known to drive differentiation and in epigenetic modifiers implicat  ...[more]

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