# DNA repair pathway choice mediates somatic cell reprogramming

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $467,106

## Abstract

Project Summary
Reprogramming is the conversion of a somatic cell to a pluripotent stem cell. This technique is now routinely
used in laboratories around the world, but the vast majority of reprogrammed stem cell lines are not
developmentally fully competent, compromising their utility in research and therapy. Reprogramming induces
DNA damage, which can have lasting consequences on the quality of the resulting cells. Our studies have
shown that DNA damage during reprogramming is induced by abnormalities in DNA replication. However, the
cause of DNA damage, the mechanisms of repair, and the developmental consequences of the damage are
not well understood. The strength of this proposal is that with the experimental systems used, we are able to
identify the specific type of damage induced by reprogramming, and the molecular mechanisms required for
repair: we are able to distinguish the role of double strand break HR from the role of stalled replication fork
stability. We are also able to distinguish the effect of genome instability on reprogramming efficiency from
incomplete transcriptional transitions. We are able to map the sites in the genome with reprogramming-induced
damage, and we are able to identify pathways that can be used to increase genome stability and potentially
improve developmental competence of reprogrammed stem cells. These studies will provide a mechanistic
understanding how genome instability inhibits the induced transition between different cellular states.

## Key facts

- **NIH application ID:** 9973944
- **Project number:** 1R01GM132604-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Dieter Meinrad Egli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $467,106
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973944

## Citation

> US National Institutes of Health, RePORTER application 9973944, DNA repair pathway choice mediates somatic cell reprogramming (1R01GM132604-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9973944. Licensed CC0.

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