# Causes and Consequences of Aneuploidy in HeSCs

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2021 · $321,282

## Abstract

PROJECT SUMMARY/ABSTRACT
During cell division chromosomes must be accurately segregated to produce daughter cells with the correct
numbers of chromosomes whereas segregation errors generate aneuploid cells with abnormal numbers of
chromosomes. In normal human somatic cells, chromosome segregation errors and aneuploidy are rare. In
contrast, in human totipotent and pluripotent embryonic cells meiotic and mitotic errors are common, resulting
in aneuploidy being the leading cause of miscarriages and birth defects. Yet, we do not understand the
mechanisms responsible for this, particularly for mitotic errors. Moreover, given such a high mitotic error rate,
it is proposed that diploid cells can outcompete aneuploid cells as development progresses to establish euploid
embryos, but how this occurs is unknown. We will address these gaps in our knowledge using pluripotent
human embryonic stem cells (hESCs) and a combination of quantitative imaging, chemical, and genomics
approaches. The specific aims of this grant are (1) to determine the mitotic pathways responsible for
chromosome segregation errors in hESCs, (2) to determine if the G1 cell cycle structure of hESCs permits an
initial tolerance to aneuploidy, and (3) to determine how an aneuploid genome subsequently impairs hESCs
contribution to embryonic tissues. Collectively, these aims test our overarching hypothesis that pluripotent
embryonic cells are inherently different from somatic cells with respect to mechanisms that support
chromosome segregation fidelity and in their response to aneuploidy. Furthermore, this work lays the
foundation for our long-term objectives of identifying the molecular signaling pathways responsible for the
causes, tolerance, and consequences of aneuploidy in embryonic cells and for developing strategies that
preserve the genome integrity of embryonic cells grown in culture to improve the success of reproductive and
regenerative medicine therapies. In conclusion, this work will reveal both the mechanisms underlying
aneuploidy in embryonic cells and how karyotype stability is eventually achieved to support normal human
development.

## Key facts

- **NIH application ID:** 10163228
- **Project number:** 5R01HD101436-02
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Kristina M Godek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $321,282
- **Award type:** 5
- **Project period:** 2020-05-12 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163228

## Citation

> US National Institutes of Health, RePORTER application 10163228, Causes and Consequences of Aneuploidy in HeSCs (5R01HD101436-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10163228. Licensed CC0.

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