Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing
<jats:title>Abstract</jats:title><jats:p>Karyotype alterations have emerged as on-target complications from CRISPR-Cas9 genome editing. However, the events that lead to these karyotypic changes in embryos after Cas9-treatment remain unknown. Here, using imaging and single-cell geno...
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2022
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| Online Access: | https://hdl.handle.net/1721.1/146846 |
| _version_ | 1826201225916317696 |
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| author | Papathanasiou, Stamatis Markoulaki, Styliani Blaine, Logan J Leibowitz, Mitchell L Zhang, Cheng-Zhong Jaenisch, Rudolf Pellman, David |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Papathanasiou, Stamatis Markoulaki, Styliani Blaine, Logan J Leibowitz, Mitchell L Zhang, Cheng-Zhong Jaenisch, Rudolf Pellman, David |
| author_sort | Papathanasiou, Stamatis |
| collection | MIT |
| description | <jats:title>Abstract</jats:title><jats:p>Karyotype alterations have emerged as on-target complications from CRISPR-Cas9 genome editing. However, the events that lead to these karyotypic changes in embryos after Cas9-treatment remain unknown. Here, using imaging and single-cell genome sequencing of 8-cell stage embryos, we track both spontaneous and Cas9-induced karyotype aberrations through the first three divisions of embryonic development. We observe the generation of abnormal structures of the nucleus that arise as a consequence of errors in mitosis, including micronuclei and chromosome bridges, and determine their contribution to common karyotype aberrations including whole chromosome loss that has been recently reported after editing in embryos. Together, these data demonstrate that Cas9-mediated germline genome editing can lead to unwanted on-target side effects, including major chromosome structural alterations that can be propagated over several divisions of embryonic development.</jats:p> |
| first_indexed | 2024-09-23T11:48:32Z |
| format | Article |
| id | mit-1721.1/146846 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:48:32Z |
| publishDate | 2022 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1468462022-12-13T03:28:00Z Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing Papathanasiou, Stamatis Markoulaki, Styliani Blaine, Logan J Leibowitz, Mitchell L Zhang, Cheng-Zhong Jaenisch, Rudolf Pellman, David Massachusetts Institute of Technology. Department of Biology <jats:title>Abstract</jats:title><jats:p>Karyotype alterations have emerged as on-target complications from CRISPR-Cas9 genome editing. However, the events that lead to these karyotypic changes in embryos after Cas9-treatment remain unknown. Here, using imaging and single-cell genome sequencing of 8-cell stage embryos, we track both spontaneous and Cas9-induced karyotype aberrations through the first three divisions of embryonic development. We observe the generation of abnormal structures of the nucleus that arise as a consequence of errors in mitosis, including micronuclei and chromosome bridges, and determine their contribution to common karyotype aberrations including whole chromosome loss that has been recently reported after editing in embryos. Together, these data demonstrate that Cas9-mediated germline genome editing can lead to unwanted on-target side effects, including major chromosome structural alterations that can be propagated over several divisions of embryonic development.</jats:p> 2022-12-12T18:28:20Z 2022-12-12T18:28:20Z 2021 2022-12-12T18:16:43Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/146846 Papathanasiou, Stamatis, Markoulaki, Styliani, Blaine, Logan J, Leibowitz, Mitchell L, Zhang, Cheng-Zhong et al. 2021. "Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing." Nature Communications, 12 (1). en 10.1038/S41467-021-26097-Y Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Papathanasiou, Stamatis Markoulaki, Styliani Blaine, Logan J Leibowitz, Mitchell L Zhang, Cheng-Zhong Jaenisch, Rudolf Pellman, David Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing |
| title | Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing |
| title_full | Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing |
| title_fullStr | Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing |
| title_full_unstemmed | Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing |
| title_short | Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing |
| title_sort | whole chromosome loss and genomic instability in mouse embryos after crispr cas9 genome editing |
| url | https://hdl.handle.net/1721.1/146846 |
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