C/EBPα creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
---|---|
Journal | Nature Cell Biology |
Volume | 18 |
Issue number | 4 |
Pages (from-to) | 371-81 |
Number of pages | 11 |
ISSN | 1465-7392 |
DOIs | |
Publication status | Published - Apr 2016 |
- Animals, B-Lymphocytes, Blotting, Western, CCAAT-Enhancer-Binding Protein-alpha, Cell Line, Cells, Cultured, Cellular Reprogramming, Female, Gene Expression Profiling, Gene Ontology, HEK293 Cells, Histone Demethylases, Humans, Induced Pluripotent Stem Cells, Kruppel-Like Transcription Factors, Male, Mice, Mice, Inbred C57BL, Mouse Embryonic Stem Cells, Nuclear Proteins, Proteomics, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Up-Regulation, Journal Article, Research Support, Non-U.S. Gov't
Research areas
ID: 167470875