Cell-of-origin specific 3D genome structure acquired during somatic cell reprogramming [Expression]

We studied genome topology dynamics during reprogramming of different somatic cell types with highly distinct genome conformations. We find large-scale 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 discerning 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. Transcriptome analysis was performed in somatic cells (NSC, macrophages, MEFs and pre-B cells) and their corresponding early and late induced pluripotent stem cells. In addition, expression analysis was performed in E14 embryonic stem cells