C/EBPα creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4
| Autor: | Janus S. Jakobsen, Francesco Limone, Bruno Di Stefano, Bo T. Porse, Mirko Francesconi, Matthias Mann, Samuel Collombet, Denis Thieffry, Carolina Segura-Morales, Michael Wierer, Jose Luis Sardina, Thomas Graf, Ralph Stadhouders, Andreas Lackner |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Proteomics Blotting Western Induced Pluripotent Stem Cells Kruppel-Like Transcription Factors Biology Cell Line 03 medical and health sciences Kruppel-Like Factor 4 Mice Downregulation and upregulation CCAAT-Enhancer-Binding Protein-alpha Animals Humans Induced pluripotent stem cell Cells Cultured Histone Demethylases Induced stem cells B-Lymphocytes Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling HEK 293 cells Nuclear Proteins Mouse Embryonic Stem Cells Cell Biology Cellular Reprogramming Cell biology Up-Regulation Mice Inbred C57BL 030104 developmental biology Gene Ontology HEK293 Cells Cell culture KLF4 Cancer research Female Signal transduction Reprogramming Transcription Factors |
| Zdroj: | Nature Cell Biology |
| ISSN: | 1476-4679 |
| Popis: | Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) is typically inefficient and has been explained by elite-cell and stochastic models. We recently reported that B cells exposed to a pulse of C/EBPα (Bα' cells) behave as elite cells, in that they can be rapidly and efficiently reprogrammed into iPSCs by the Yamanaka factors OSKM. Here we show that C/EBPα post-transcriptionally increases the abundance of several hundred proteins, including Lsd1, Hdac1, Brd4, Med1 and Cdk9, components of chromatin-modifying complexes present at super-enhancers. Lsd1 was found to be required for B cell gene silencing and Brd4 for the activation of the pluripotency program. C/EBPα also promotes chromatin accessibility in pluripotent cells and upregulates Klf4 by binding to two haematopoietic enhancers. Bα' cells share many properties with granulocyte/macrophage progenitors, naturally occurring elite cells that are obligate targets for leukaemic transformation, whose formation strictly requires C/EBPα. |
| Databáze: | OpenAIRE |
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