title: Cell-of-Origin-Specific 3D Genome Structure Acquired during Somatic Cell Reprogramming.
abstract: Forced expression of reprogramming factors can convert somatic cells into induced pluripotent stem cells (iPSCs). Here we studied genome topology dynamics during reprogramming of different somatic cell types with highly distinct genome conformations. We find large-scale topologically associated domain (TAD) repositioning and alterations of tissue-restricted genomic neighborhoods and chromatin loops, effectively erasing the somatic-cell-specific genome structures while establishing an embryonic stem-cell-like 3D genome. Yet, early passage iPSCs carry topological hallmarks that enable recognition of their cell of origin. These hallmarks are not remnants of somatic chromosome topologies. Instead, the distinguishing topological features are acquired during reprogramming, as we also find for cell-of-origin-dependent gene expression patterns.
authors.affiliation: Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Peter Hugo Lodewijk
authors.initials: PH
authors.lastname: Krijger
authors.affiliation: Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG) and Pompeu Fabra University, Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Di Stefano
authors.affiliation: Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Elzo
authors.initials: E
authors.lastname: de Wit
authors.affiliation: Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG) and Pompeu Fabra University, Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Francesco
authors.initials: F
authors.lastname: Limone
authors.affiliation: Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG) and Pompeu Fabra University, Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Chris
authors.initials: C
authors.lastname: van Oevelen
authors.affiliation: Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands. Electronic address: w.delaat@hubrecht.eu.
authors.forename: Wouter
authors.initials: W
authors.lastname: de Laat
authors.affiliation: Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG) and Pompeu Fabra University, Dr Aiguader 88, 08003 Barcelona, Spain. Electronic address: thomas.graf@crg.eu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Graf
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics*; D002843:Chromatin / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000737:chemistry; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D051379:Mice; D008954:Models, Biological; D009928:Organ Specificity / Q000235:genetics*
chemical_list: D002843:Chromatin