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Exploring and validating the marmoset as a primate model for chromosomal instability in early development
Andrew Cearlock1,2, Hubert Mysliwiec3, Margarita Agarsheva3
1Department of Obstetrics & Gynecology, University of Washington, Seattle, WA, USA.
Molecular Human Reproduction
|April 7, 2025
Summary
Marmosets reveal conserved mechanisms of embryonic aneuploidy, or chromosomal instability (CIN), in primates. Naïve-like stem cells offer a new model for studying genomic instability during early development.
Area of Science:
- Developmental Biology
- Genetics
- Reproductive Biology
Background:
- Aneuploidy, or abnormal chromosome number, is a major cause of early miscarriages and developmental issues.
- Understanding the molecular basis of aneuploidy in human embryos is limited by ethical concerns and inadequate animal models.
- Chromosomal instability (CIN) is a hallmark of many cancers and developmental abnormalities.
Purpose of the Study:
- To identify and characterize aneuploidy in early primate development using a novel animal model.
- To establish a pluripotent stem cell line from marmosets for studying early embryonic cell fate.
- To investigate the molecular pathways and developmental consequences of aneuploidy in primate embryos.
Main Methods:
- Single-cell RNA-sequencing to detect copy number variants and assess aneuploidy in marmoset embryonic cells.
- Gastruloid differentiation to observe lineage-specific behavior of aneuploid cells.
- Generation and characterization of naïve-like marmoset pluripotent stem cells (cjPSCs).
- Transcriptome analysis to identify molecular pathways associated with aneuploidy.
Main Results:
- Marmoset preimplantation embryos exhibit heterogeneous aneuploidy and chromosomal instability (CIN).
- Marmoset aneuploidy shows lineage-specific behavior during gastruloid differentiation, mirroring human development.
- Naïve-like cjPSCs possess inherent CIN and serve as a model for early specification.
- Downregulation of cell cycle checkpoints and upregulation of autophagy are linked to aneuploidy.
- Spontaneous aneuploidy in cjPSCs did not affect blastoid formation, but enhanced cavity formation, suggesting post-gastrulation sensitivity.
Conclusions:
- The marmoset is a suitable model for studying CIN in early primate development.
- Conserved regulatory mechanisms for lineage specification in the presence of aneuploidy exist between marmosets and humans.
- Naïve-like cjPSCs provide a robust system for investigating aneuploid cell fates in vivo.
- Aneuploidy's consequences in primate development may become more apparent after gastrulation.
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