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Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17016-21. doi: 10.1073/pnas.1112169108. Epub 2011 Oct 3.

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

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Cancer and Differentiation Program, Center for Genomic Regulation and Pompeu Fabra University, 08003 Barcelona, Spain.

Erratum in

  • Proc Natl Acad Sci U S A. 2012 Jul 3;109(27):11053.
  • Proc Natl Acad Sci U S A. 2012. doi: 10.1073/pnas.1208762109. Castellano, Giancarlo [added].


Earlier work has shown that pre-B cells can be converted into macrophages by the transcription factor CCAAT/enhancer binding protein α at very high frequencies. Using this system, we performed a systematic analysis of whether during transdifferentiation the cells transiently reactivate progenitor-restricted genes or even retrodifferentiate. A transcriptome analysis of transdifferentiating cells showed that most genes are up- or down-regulated continuously, acquiring a macrophage phenotype within 5 d. In addition, we observed the transient reactivation of a subset of immature myeloid markers, as well as low levels of the progenitor markers Kit and FMS-like tyrosine kinase 3 and a few lineage-inappropriate genes. Importantly, however, we were unable to observe the reexpression of cell-surface marker combinations that characterize hematopoietic stem and progenitor cells, including c-Kit and FMS-like tyrosine kinase 3, even when CAAT/enhancer binding protein α was activated in pre-B cells under culture conditions that favor growth of hematopoietic stem and progenitor cells or when the transcription factor was activated in a time-limited fashion. Together, our findings are consistent with the notion that the conversion from pre-B cells to macrophages is mostly direct and does not involve overt retrodifferentiation.

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