Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing
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s41467-021-26097-y.pdf
Description
Published version
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10.23 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Papathanasiou, Stamatis
Markoulaki, Styliani
Blaine, Logan J
Leibowitz, Mitchell L
Zhang, Cheng-Zhong
Jaenisch, Rudolf
Pellman, David
Date Issued
2021
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
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).
Version
Final published version
Abstract
AbstractKaryotype 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/S41467-021-26097-Y
