Evidence map›Paper›PMID 34615869›Full record

ArticleNature communications2021

Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing.

Stamatis Papathanasiou, Styliani Markoulaki, Logan J Blaine, Mitchell L Leibowitz, Cheng-Zhong Zhang, Rudolf Jaenisch, David Pellman

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
9.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

83 citing papers in PubMed, 137 citations in OpenAlex.

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  20. Chromosomal Instability and Chromoanagenesis as Forces for Genomic Evolution.Methods in molecular biology (Clifton, N.J.) · 2025
    Review

23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Stamatis PapathanasiouDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-6969-044X
Styliani Markoulaki *Whitehead Institute, Cambridge, MA, USA.
Logan J Blaine *Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0937-9216
Mitchell L LeibowitzDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-1874-5441
Cheng-Zhong ZhangDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-8825-7158
Rudolf JaenischWhitehead Institute, Cambridge, MA, USA. jaenisch@wi.mit.edu.ORCID 0000-0002-2540-7099
David PellmanDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. david_pellman@dfci.harvard.edu.ORCID 0000-0001-5306-8031
Harvard University · USHoward Hughes Medical Institute · USWhitehead Institute for Biomedical Research · US

Funding

Virology Core: MIT Center for Human Tissue Models for Infectious Diseases (MIT.HTMID)U19AI131135 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GEHRKE, LEE · 2017 to 2021
$8.7M
Transcriptional condensates, epigenetic editing and Rett SyndromeR01MH104610 · NIMH · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF, YOUNG, RICHARD · 2014 to 2023
$7.4M
Polyploidy, Aneuploidy and Genome StabilityR01CA213404 · NCI · DANA-FARBER CANCER INST · PI PELLMAN, DAVID S · 2017 to 2024
$3.5M
Single-cell analysis of mutagenesis: from mutational mechanisms to functional consequencesK22CA216319 · NCI · DANA-FARBER CANCER INST · PI ZHANG, CHENG-ZHONG · 2017 to 2019
$596k
Howard Hughes Medical InstituteNCI NIH HHS K22 CA216319NCI NIH HHS R01 CA213404NIAID NIH HHS U19 AI131135NIMH NIH HHS R01 MH104610
6 · The paper itself

Abstract

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.

Indexed as

Chromosome StructuresCRISPR-Cas SystemsGenomic InstabilityAnimalsChromosome SegregationEmbryo, MammalianEmbryonic DevelopmentGene EditingKaryotypeMiceWhole Genome Sequencing

Identifiers

PMID34615869
PMCPMC8494802
OpenAlexW3201670395

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.