Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Promotion of Direct Reprogramming by Glis1


ABSTRACT: Induced pluripotent stem cells (iPSC) are generated from somatic cells by the transgene expression of three transcription factors Oct3/4, Sox2, and Klf4 (OSK), albeit at a low efficiency. The protooncogene c-Myc enhances the efficiency of iPSC generation by OSK, but it also increases the tumorigenicity of the resulting iPSC. In the current study, we found the Gli-like transcription factor Glis1, when expressed together with OSK, to markedly enhance the generation of iPSC from both mouse and human fibroblasts. Mouse iPSC generated by OSK and Glis1 can form germline-competent chimeras. Glis1 is enriched in unfertilized oocytes and one cell-stage embryos. DNA microarray analyses revealed that Glis1 promotes multiple pro-reprogramming pathways, including Myc, Nanog, Lin28, Wnt, mesenchymal-epithelial transition (MET), and Esrrb. These results therefore demonstrated that oocyte transcription factor Glis1 effectively promote direct reprogramming during iPSC generation. p53-null mouse embryonic fibroblasts were transduced with OSK and OSK+Glis1 and were used for microarray analyses.

ORGANISM(S): Mus musculus

SUBMITTER: Shinya Yamanaka 

PROVIDER: E-GEOD-26429 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1.

Maekawa Momoko M   Yamaguchi Kei K   Nakamura Tomonori T   Shibukawa Ran R   Kodanaka Ikumi I   Ichisaka Tomoko T   Kawamura Yoshifumi Y   Mochizuki Hiromi H   Goshima Naoki N   Yamanaka Shinya S  

Nature 20110608 7350


Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the transgenic expression of three transcription factors collectively called OSK: Oct3/4 (also called Pou5f1), Sox2 and Klf4. However, the conversion to iPSCs is inefficient. The proto-oncogene Myc enhances the efficiency of iPSC generation by OSK but it also increases the tumorigenicity of the resulting iPSCs. Here we show that the Gli-like transcription factor Glis1 (Glis family zinc finger 1) markedly enhances the gene  ...[more]

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