GEO series
Minimizing far-extending chromatin perturbation in genome editing preserves stem cell identity [Cut&Tag]
GSE320165
Homo sapiens; Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
46 samples
Submitted 2026/02/26
Platform GPL28330Platform GPL29480
Summary
While CRISPR/Cas9 holds therapeutic promise, broader application demands understanding complications in vast non-coding regions. We found that CRISPR/Cas9 can cause premature differentiation of neural stem cells in vivo and mouse embryonic stem cells in vitro, even when cleavage occurred at distant sites tens of kilobases away from the nearest regulatory elements. To investigate this, we employed an integrated ATAC/RNA approach (AR-seq) and identified editing-induced chromatin accessibility change, with its scale varying by cell types. Cells with stemness are most affected, experiencing perturbations that extend over a hundred kilobases. Furthermore, even local DNA perturbations can disrupt CTCF- and condensate-associated chromatin architecture, causing distal transcriptional rewiring and ultimately loss of stemness identity. To minimize chromatin perturbations and preserve cell identity we refined gene editing strategies, including distance-aware sgRNA design, pharmacological attenuation of DNA resection, and alternative editing systems. This work paves the way for safer and broader application of genome editing technologies.
Published in
Zhu M, Yuan J, Meng Q et al.
· Cell stem cell 2026
· PMID 41742419
· doi:10.1016/j.stem.2026.01.015
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE320165_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 46 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1426990 and SRA study SRP678688. Searching any of these in the dataset finder brings you back here.
Study design
20 conditions, mostly in duplicate
CUT&Tag hek293t_emx1_h3k27ac ×2
CUT&Tag hek293t_emx1_h3k27me3 ×2
CUT&Tag hek293t_emx1_h3k9me3 ×2
CUT&Tag hek293t_wt_h3k27ac ×2
CUT&Tag hek293t_wt_h3k27me3 ×2
CUT&Tag hek293t_wt_h3k9me3 ×2
CUT&Tag hek293t_zswim3_h3k27ac ×2
CUT&Tag hek293t_zswim3_h3k27me3 ×2
+12 more
Supports a between-group comparison across 40 samples.
20 replicated groups read from the first 40 of 46 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9536668 CUT&Tag hek293t_emx1_h3k27ac_rep1
- GSM9536669 CUT&Tag hek293t_emx1_h3k27ac_rep2
- GSM9536670 CUT&Tag hek293t_emx1_h3k27me3_rep1
- GSM9536671 CUT&Tag hek293t_emx1_h3k27me3_rep2
- GSM9536672 CUT&Tag hek293t_emx1_h3k9me3_rep1
- GSM9536673 CUT&Tag hek293t_emx1_h3k9me3_rep2
- GSM9536674 CUT&Tag hek293t_wt_h3k27ac_rep1
- GSM9536675 CUT&Tag hek293t_wt_h3k27ac_rep2
- GSM9536676 CUT&Tag hek293t_wt_h3k27me3_rep1
- GSM9536677 CUT&Tag hek293t_wt_h3k27me3_rep2
- GSM9536678 CUT&Tag hek293t_wt_h3k9me3_rep1
- GSM9536679 CUT&Tag hek293t_wt_h3k9me3_rep2
- GSM9536680 CUT&Tag hek293t_zswim3_h3k27ac_rep1
- GSM9536681 CUT&Tag hek293t_zswim3_h3k27ac_rep2
- GSM9536682 CUT&Tag hek293t_zswim3_h3k27me3_rep1
- GSM9536683 CUT&Tag hek293t_zswim3_h3k27me3_rep2
- GSM9536684 CUT&Tag hek293t_zswim3_h3k9me3_rep1
- GSM9536685 CUT&Tag hek293t_zswim3_h3k9me3_rep2
- GSM9536686 CUT&Tag mesc_emx1_ctcf_rep1
- GSM9536687 CUT&Tag mesc_emx1_ctcf_rep2
- GSM9536688 CUT&Tag mesc_nanog_ctcf_rep1
- GSM9536689 CUT&Tag mesc_nanog_ctcf_rep2
- GSM9536690 CUT&Tag mesc_nanogse_ctcf_rep1
- GSM9536691 CUT&Tag mesc_nanogse_ctcf_rep2
- GSM9536692 CUT&Tag mesc_pou5f1_ctcf_rep1
- GSM9536693 CUT&Tag mesc_pou5f1_ctcf_rep2
- GSM9536694 CUT&Tag mesc_tcf19_ctcf_rep1
- GSM9536695 CUT&Tag mesc_tcf19_ctcf_rep2
- GSM9536696 CUT&Tag nih3t3_emx1_h3k27ac_rep1
- GSM9536697 CUT&Tag nih3t3_emx1_h3k27ac_rep2
- GSM9536698 CUT&Tag nih3t3_emx1_h3k27me3_rep1
- GSM9536699 CUT&Tag nih3t3_emx1_h3k27me3_rep2
- GSM9536700 CUT&Tag nih3t3_emx1_h3k9me3_rep1
- GSM9536701 CUT&Tag nih3t3_emx1_h3k9me3_rep2
- GSM9536702 CUT&Tag nih3t3_wt_h3k27ac_rep1
- GSM9536703 CUT&Tag nih3t3_wt_h3k27ac_rep2
- GSM9536704 CUT&Tag nih3t3_wt_h3k27me3_rep1
- GSM9536705 CUT&Tag nih3t3_wt_h3k27me3_rep2
- GSM9536706 CUT&Tag nih3t3_wt_h3k9me3_rep1
- GSM9536707 CUT&Tag nih3t3_wt_h3k9me3_rep2
+ 6 more — browse all 46 samples with per-sample file links →
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