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Series GSE261864 Query DataSets for GSE261864
Status Public on Sep 24, 2024
Title Transfer of mitochondrial DNA into the nuclear genome during gene editing [PEM-Seq MT stress]
Organism Homo sapiens
Experiment type Other
Summary Mitochondria serve as the cellular powerhouse, and their distinct DNA makes them a prospective target for gene editing to treat genetic disorders. However, the impact of genome editing on mitochondrial DNA (mtDNA) stability remains a mystery. Our study reveals previously unknown risks of genome editing that both nuclear and mitochondrial editing cause broad transfer of mitochondrial DNA segments into the nuclear genome in various cell types including human cell lines, primary T cells, and mouse embryos. Furthermore, drug-induced mitochondrial stresses and mtDNA breaks exacerbate this transfer of mtDNA into the nuclear genome. Notably, we observe that mitochondrial targeting editors, mitoTALEN and recently developed base editor DdCBE, can also induce widespread mtDNA integrations. However, we provide a practical solution to suppress mtDNA transfer by co-expressing TREX1 or TREX2 exonucleases during DdCBE editing. These findings also shed light on the origins of mitochondrial-nuclear DNA segments.
 
Overall design We employed primer-extension-mediated sequencing (PEM-seq) to study the level of mitochondrial DNA integration into the nuclear genome caused by genome editing.
 
Contributor(s) Wu J, Liu Y, Ou L, Gan T, Zhangding Z, Yuan S, Liu X, Liu M, Li J, Yin J, Xin C, Tian Y, Hu J
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Submission date Mar 18, 2024
Last update date Sep 25, 2024
Contact name Jinchun Wu
E-mail(s) wujinchun@pku.edu.cn
Phone 13124791092
Organization name Peking University
Street address No. 5, Yiheyuan street
City Beijing
ZIP/Postal code 100871
Country China
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (9)
GSM8153204 HU109_JC278a_c.MYC_spCas9_control.for.MTstress_rp1
GSM8153205 HU109_JC278b_c.MYC_spCas9_control.for.MTstress_rp2
GSM8153206 HU109_JC278c_c.MYC_spCas9_control.for.MTstress_rp3
This SubSeries is part of SuperSeries:
GSE226884 Gene editing induces the transfer of mitochondrial DNA into the nuclear genome
Relations
BioProject PRJNA1089224

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Supplementary file Size Download File type/resource
GSE261864_RAW.tar 33.9 Mb (http)(custom) TAR (of TAB)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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