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C/EBPα creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4
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C/EBPα creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4
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Journal Article
C/EBPα creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4
2016
Overview
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.
Graf and colleagues find that B cells exposed to a pulse of C/EBPα and the Yamanaka factors convert into elite-type cells that rapidly and efficiently reprogram into iPSCs, in a process that involves upregulation of Lsd1, Brd4 and Klf4.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
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/ Animals
/ CCAAT-Enhancer-Binding Protein-alpha - genetics
/ CCAAT-Enhancer-Binding Protein-alpha - metabolism
/ Cellular Reprogramming - genetics
/ Female
/ Gene Expression Profiling - methods
/ Growth
/ Histone Demethylases - genetics
/ Histone Demethylases - metabolism
/ Humans
/ Induced Pluripotent Stem Cells - metabolism
/ Kruppel-Like Transcription Factors - genetics
/ Kruppel-Like Transcription Factors - metabolism
/ Male
/ Mice
/ Mouse Embryonic Stem Cells - metabolism
/ Nuclear Proteins - metabolism
/ Reverse Transcriptase Polymerase Chain Reaction
/ Transcription Factors - genetics
