# Characterization of aneuploidy, cell fate and mosaicism in early development

> **NIH NIH R00** · UNIVERSITY OF WASHINGTON · 2024 · $229,562

## Abstract

PROJECT SUMMARY
The presence of aneuploidy (chromosomal abnormalities) in embryos is considered one of the major limitations
to successful human reproduction and a significant cause of gestation failure, accounting for approximately 50%
of early miscarriages. Aneuploidy rates are strikingly high in in vitro fertilized human embryos, and around 60%
of these embryos are mosaic, containing both aneuploid and normal euploid cells. The frequent occurrence of
mosaicism exists in both naturally conceived and IVF pregnancies. However, despite the high incidence of
aneuploidy in human embryos, our knowledge of the molecular mechanisms and developmental fate of these
cells is restricted due to the considerable ethical limitations associated with human embryo and fetal research.
My previous work demonstrated lineage-specific behavior of aneuploidy in early differentiation using an in vitro
human embryonic stem cell (hESC) model. To further characterize the cellular physiology of aneuploidy after
implantation, an in vivo animal model is required. Common marmosets exhibit naturally occurring aneuploidy,
making them a more representative model for humans than rodents are. Therefore, I propose a marmoset model
to further dissect aneuploidy cell fate and its molecular and cellular consequences during early development. My
preliminary data uncovered that aneuploid marmoset embryonic stem cells (cj-ESCs) preferentially differentiate
into trophectoderm lineages in response to BMP4 stimulation, similar to the behavior I observed with hESCs in
my previous work, suggesting a conserved role of aneuploidy in restricting stem cells to extraembryonic fates.
During the training period, I will use a unique marmoset stem cell model (gastruloid) that recapitulates early
lineage specification and gastrulation to investigate the role of BMP4 signaling in the phenotypic manifestation
of aneuploidy (Aim 1). To further investigate the elimination and allocation of aneuploidy, I will construct mosaic
marmoset embryos to probe aneuploidy cell fate and behaviors during pre-and post-implantation embryonic
development in vitro (Aim 2). Since my preliminary data indicates a higher tolerance of aneuploidy in the
extraembryonic lineages, during the independent phase of the award period, I propose to analyze the gene
expression profile of aneuploidy in the marmoset placenta to understand the effects of aneuploidy on the cellular
physiology of extraembryonic tissue. In addition, during this phase, I will construct a placental/trophoblast
organoid from cj-ESCs to further dissect the behaviors of aneuploidy in different placental lineages (Aim 3).
Together, the proposed research will present a comprehensive model for studying a previously uncharacterized
mechanism underlying the elimination of aneuploidy during embryogenesis, paving the way for translational
applications to assisted reproductive technologies. The proposed project will also serve as a platform for me to
obtain training and sci...

## Key facts

- **NIH application ID:** 10899618
- **Project number:** 5R00HD107219-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Min Yang
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $229,562
- **Award type:** 5
- **Project period:** 2023-08-04 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899618

## Citation

> US National Institutes of Health, RePORTER application 10899618, Characterization of aneuploidy, cell fate and mosaicism in early development (5R00HD107219-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10899618. Licensed CC0.

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