title: CCAAT/enhancer binding protein alpha (C/EBP(alpha))-induced transdifferentiation of pre-B cells into macrophages involves no overt retrodifferentiation.
abstract: 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.
authors.affiliation: Cancer and Differentiation Program, Center for Genomic Regulation and  Pompeu Fabra University, 08003 Barcelona,  Spain.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Di Tullio
authors.forename: Thien Phong
authors.initials: TP
authors.lastname: Vu Manh
authors.forename: Alexis
authors.initials: A
authors.lastname: Schubert
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Castellano
authors.forename: Robert
authors.initials: R
authors.lastname: Månsson
authors.forename: Thomas
authors.initials: T
authors.lastname: Graf
mesh_terms: D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage / Q000235:genetics; D054338:Cell Transdifferentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D018816:Genes, cdc; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D059467:Transcriptome; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D012333:RNA, Messenger; C497971:Flt3 protein, mouse; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3