title: A robust and highly efficient immune cell reprogramming system.
abstract: Here we describe a lineage reprogramming system consisting of a B cell line with an estradiol-inducible form of C/EBPalpha where cells can be converted into macrophage-like cells at 100% efficiency within 2 to 3 days. The reprogrammed cells are larger, contain altered organelle and cytoskeletal structures, are phagocytic, and exhibit an inflammatory response. Time-lapse experiments showed that the cells acquire a macrophage morphology and increased migratory activity as early as 10 hr. During induction, thousands of genes become up- or downregulated, including several dozen transcription and chromatin-remodeling factors. Time-limited exposure of cells to the inducer showed that the reprogrammed cells become transgene independent within 1 to 2 days. The reprogramming can be inhibited, at least partially, by perturbation experiments with B cell and macrophage transcription factors. The tightness, robustness, and speed of the system described make it a versatile tool to study biochemical and biological aspects of lineage reprogramming.
authors.affiliation: Center for Genomic Regulation and Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Bussmann
authors.forename: Alexis
authors.initials: A
authors.lastname: Schubert
authors.forename: Thien Phong
authors.initials: TP
authors.lastname: Vu Manh
authors.forename: Luisa
authors.initials: L
authors.lastname: De Andres
authors.forename: Sabrina C
authors.initials: SC
authors.lastname: Desbordes
authors.forename: Maribel
authors.initials: M
authors.lastname: Parra
authors.forename: Timo
authors.initials: T
authors.lastname: Zimmermann
authors.forename: Francesca
authors.initials: F
authors.lastname: Rapino
authors.forename: Javier
authors.initials: J
authors.lastname: Rodriguez-Ubreva
authors.forename: Esteban
authors.initials: E
authors.lastname: Ballestar
authors.forename: Thomas
authors.initials: T
authors.lastname: Graf
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D054338:Cell Transdifferentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D050656:Transcription Factor AP-2; D015533:Transcriptional Activation; D014161:Transduction, Genetic
chemical_list: D000943:Antigens, Differentiation; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D018836:Inflammation Mediators; D011993:Recombinant Fusion Proteins; C493668:Tfap2a protein, mouse; D050656:Transcription Factor AP-2; D004958:Estradiol