C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells

  title={C/EBP$\alpha$ poises B cells for rapid reprogramming into induced pluripotent stem cells},
  author={Bruno Di Stefano and Jos{\'e} Luis Sardina and Chris van Oevelen and Samuel Collombet and Eric M. Kallin and Guillermo P Vicent and Jun Lu and Denis Thieffry and Miguel Beato and Thomas Graf},
CCAAT/enhancer binding protein-α (C/EBPα) induces transdifferentiation of B cells into macrophages at high efficiencies and enhances reprogramming into induced pluripotent stem (iPS) cells when co-expressed with the transcription factors Oct4 (Pou5f1), Sox2, Klf4 and Myc (hereafter called OSKM). However, how C/EBPα accomplishes these effects is unclear. Here we find that in mouse primary B cells transient C/EBPα expression followed by OSKM activation induces a 100-fold increase in iPS cell… 

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

It is shown 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.

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A transient interval soon after pluripotency exit that permits high-efficiency reprogramming and is facilitated by OCT4 bound elements displaying unique silencing behaviour during differentiation is identified.

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The multifaceted functions of C/EBPα in normal and malignant haematopoiesis

The current knowledge on the functions of C/EBPα during normal and malignant haematopoiesis with special emphasis on the recent work is summarized.

Trib2 regulates the pluripotency of embryonic stem cells and enhances reprogramming efficiency

The results suggest that Trib2 is important for maintaining self-renewal in ES cells and for pluripotency induction during the reprogramming process.

Directed Evolution of an Enhanced POU Reprogramming Factor for Cell Fate Engineering

An artificially evolved and enhanced POU factor (ePOU) is identified that substantially outperforms wild-type Oct4 in terms of reprogramming speed and efficiency and demonstrates that the phenotypic selection of novel factor variants from mammalian cells with desired properties is key to advancing cell fate conversions with artificially evolved biomolecules.

Time-resolved gene expression profiling during reprogramming of C/EBPα-pulsed B cells into iPS cells

A dataset containing the time course of gene expression during the reprogramming of somatic cells to induced pluripotent stem cells as determined by microarray and RNA-seq techniques is presented.



C/EBPα bypasses cell cycle-dependency during immune cell transdifferentiation

The data show that traversing the cell cycle is not strictly required for pre-B cell to macrophage conversion and provides new evidence for the notion that the mechanisms of transcription factor induced transdifferentiation and iPS cell reprogramming differ.

Deterministic direct reprogramming of somatic cells to pluripotency

The findings uncover a dichotomous molecular function for the reprogramming factors, serving to reactivate endogenous pluripotency networks while simultaneously directly recruiting the Mbd3/NuRD repressor complex that potently restrains the reactivation of OSKM downstream target genes.

CCAAT/enhancer binding protein α (C/EBPα)-induced transdifferentiation of pre-B cells into macrophages involves no overt retrodifferentiation

The findings are consistent with the notion that the conversion from pre-B cells to macrophages is mostly direct and does not involve overt retrodifferentiation.

Direct cell reprogramming is a stochastic process amenable to acceleration

Quantitative analyses define distinct cell-division-rate-dependent and -independent modes for accelerating the stochastic course of reprogramming, and suggest that the number of cell divisions is a key parameter driving epigenetic reprograming to pluripotency.

PU.1 and C/EBPα/β convert fibroblasts into macrophage-like cells

The data suggest that it might become possible to induce the transdifferentiation of skin-derived fibroblasts into cell types desirable for tissue regeneration, and the effects of PU.1 and C/EBPα on fibro Blasts are examined.