C/EBPα creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4

Bruno Di Stefano*, Samuel Collombet, Janus Schou Jakobsen, Michael Wierer, Jose Luis Sardina, Andreas Lackner, Ralph Stadhouders, Carolina Segura-Morales, Mirko Francesconi, Francesco Limone, Matthias Mann, Bo Porse, Denis Thieffry, Thomas Graf*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

64 Citations (Scopus)

Abstract

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 languageEnglish
Pages (from-to)371-381
Number of pages11
JournalNature Cell Biology
Volume18
Issue number4
DOIs
Publication statusPublished - 14 Mar 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Macmillan Publishers Limited.

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