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Series GSE159297 Query DataSets for GSE159297
Status Public on Aug 11, 2023
Title Transient naive reprogramming corrects hiPS cells functionally and epigenetically
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Cells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ significantly, which affects hiPS cell function. These differences include epigenetic memory and aberrations that emerge during reprogramming, for which the mechanisms remain unknown. Here we characterized the persistence and emergence of these epigenetic differences by performing genome-wide DNA methylation profiling throughout primed and naive reprogramming of human somatic cells to hiPS cells. We found that reprogramming-induced epigenetic aberrations emerge midway through primed reprogramming, whereas DNA demethylation begins early in naive reprogramming. Using this knowledge, we developed a transient-naive-treatment (TNT) reprogramming strategy that emulates the embryonic epigenetic reset. We show that the epigenetic memory in hiPS cells is concentrated in cell of origin-dependent repressive chromatin marked by H3K9me3, lamin-B1 and aberrant CpH methylation. TNT reprogramming reconfigures these domains to a hES cell-like state and does not disrupt genomic imprinting. Using an isogenic system, we demonstrate that TNT reprogramming can correct the transposable element overexpression and differential gene expression seen in conventional hiPS cells, and that TNT-reprogrammed hiPS and hES cells show similar differentiation efficiencies. Moreover, TNT reprogramming enhances the differentiation of hiPS cells derived from multiple cell types. Thus, TNT reprogramming corrects epigenetic memory and aberrations, producing hiPS cells that are molecularly and functionally more similar to hES cells than conventional hiPS cells. We foresee TNT reprogramming becoming a new standard for biomedical and therapeutic applications and providing a novel system for studying epigenetic memory.

This SuperSeries is composed of the SubSeries listed below.
Overall design Refer to individual Series
Citation(s) 37587336
Submission date Oct 09, 2020
Last update date Oct 25, 2023
Contact name Ryan Lister
Phone 61864884407
Organization name The University of Western Australia
Street address 35 Stirling Highway
City Perth
State/province WA
ZIP/Postal code 6009
Country Australia
Platforms (5)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL24106 MinION (Homo sapiens)
Samples (110)
GSM4819713 ESC_MEL1_P13plus20
GSM4819714 ESC_MEL1_P13plus14
GSM4819715 Naive_MEL1_P15
This SuperSeries is composed of the following SubSeries:
GSE159114 Transient naive reprogramming corrects hiPS cells functionally and epigenetically [RNA-Seq]
GSE159296 Transient naive reprogramming corrects hiPS cells functionally and epigenetically [WGBS]
GSE159718 Transient naive reprogramming corrects hiPS cells functionally and epigenetically [ChIP-seq]
BioProject PRJNA668312

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE159297_RAW.tar 233.1 Gb (http)(custom) TAR (of BIGWIG, CGMAP, H5, TAR)
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