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| Status |
Public on Sep 24, 2024 |
| Title |
Transfer of mitochondrial DNA into the nuclear genome during gene editing [CBE_ND4 PEM-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| 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.
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| 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.
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| 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 |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Nov 22, 2023 |
| Last update date |
Sep 25, 2024 |
| Contact name |
Jinchun Wu |
| E-mail(s) |
wujinchun@pku.edu.cn
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| Phone |
13124791092
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| Organization name |
Peking University
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| Street address |
No. 5, Yiheyuan street
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| City |
Beijing |
| ZIP/Postal code |
100871 |
| Country |
China |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE226884 |
Gene editing induces the transfer of mitochondrial DNA into the nuclear genome |
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| Relations |
| BioProject |
PRJNA1044149 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE248509_RAW.tar |
260.0 Kb |
(http)(custom) |
TAR (of TAB) |
SRA Run Selector |
| Raw data are available in SRA |
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