Cell-of-Origin-Specific 3D Genome Structure Acquired during Somatic Cell Reprogramming

Peter Hugo Lodewijk Krijger, Bruno Di Stefano, Elzo de Wit, Francesco Limone, Chris van Oevelen, Wouter de Laat, Thomas Graf

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)597-610
Aantal pagina's14
TijdschriftCell Stem Cell
Volume18
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - 05 mei 2016

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