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Series GSE161633 Query DataSets for GSE161633
Status Public on Dec 31, 2022
Title Cas9 interactions with host RNAs and transposable elements impair neurodevelopment (CUT&Tag)
Organism Homo sapiens
Experiment type Other
Summary The CRISPR (clustered regulatory interspaced short palindromic repeats)/ Cas9 (CRISPR-associated protein 9) system-based precise genome editing has revolutionized biomedical studies. As the CRISPR/Cas9 system has been also recently considered to permanently cure genetic diseases via human germline genome editing, a careful risk assessment of this genome engineering tool is required in human early development. Here we perform comprehensive analysis to evaluate the potential impact of Cas9 in human early embryogenesis. We find that even in the absence of synthetic guide RNA, Cas9 can be still guided by endogenous RNAs, and cut the genome of human embryonic cells at low frequency, and the resulting DNA damage induces the intrinsic immune response. Moreover, Cas9 interferes with the spliceosome, and with the suppressor machinery (e.g. L1TD1, APOBEC3G and PIWIL4) of LINE-1 (L1) retrotransposition. Even the transient presence of Cas9 in human embryonic cells induces robust de novo L1 retrotransposition that exacerbates DNA damage, and results in compromised neurodevelopment. Besides the ethical issues, these inevitable and detrimental Cas9-associated impacts on human embryonic development raise such serious safety concerns as to question the clinical use of human germline genome editing.
Overall design We investigated Cas9 and MRE11-binding profiles on the genome of Cas9-expressing hESCs using CUT&Tag. CUT&Tag was performed in two biological replicates of hESC_WT, hESC_iCas9 and hESC_idCas9 (under doxycycline treatment or not) with the indicated antibody and IgG as control.
Contributor(s) Hu Y, Li R, Sun C, Yang M, Yu H, Chen D, Wang J
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Submission date Nov 17, 2020
Last update date Dec 31, 2022
Contact name Denghui Chen
Organization name Sun Yat-sen University
Department Zhongshan School of Medicine
Street address No. 74 Zhongshan 2nd Road
City Guangzhou City
ZIP/Postal code 510080
Country China
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (16)
GSM4911574 iCas9-Cas9 rep1
GSM4911575 iCas9-Cas9 rep2
GSM4911576 iCas9-IgG rep1
This SubSeries is part of SuperSeries:
GSE161635 Cas9 interactions with host RNAs and transposable elements impair neurodevelopment
BioProject PRJNA678978
SRA SRP292922

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

Supplementary file Size Download File type/resource
GSE161633_WT-MRE_narrowpeaks_ucsc.bed.gz 7.1 Kb (ftp)(http) BED
GSE161633_d-Cas9_narrowpeaks_ucsc.bed.gz 4.2 Kb (ftp)(http) BED
GSE161633_d-MRE_narrowpeaks_ucsc.bed.gz 10.5 Kb (ftp)(http) BED
GSE161633_i-Cas9_narrowpeaks_ucsc.bed.gz 2.4 Kb (ftp)(http) BED
GSE161633_i-Cas9_overlapped_with_i-MRE11_narrowpeaks_ucsc.bed.gz 860 b (ftp)(http) BED
GSE161633_i-MRE11_narrowpeaks_ucsc.bed.gz 12.8 Kb (ftp)(http) BED
GSE161633_iCas9_group_filtered_blender_hits.txt.gz 1.7 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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