# Transcriptome reprogramming in the early embryo

> **NIH NIH R35** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $359,164

## Abstract

Early in development, a highly coordinated maternal-to-zygotic transition “reprograms” the embryo to a
pluripotent cellular identity, capable of giving rise to all subsequent cell types in the developing organism. How
cells are induced to pluripotency is still poorly understood, and yet has enormous implications, not only for
understanding fundamental developmental and gene regulatory processes, but also for disease modeling and
therapies. The long-term goal is to decipher mechanisms and principles conserved across vertebrates that
guide pluripotency induction. To begin to address this question, this proposal aims to elucidate how
pluripotency factors provided to the egg activate the first genes from the embryonic genome in the model
vertebrate zebrafish. Zebrafish produce large clutches of externally developing embryos and express many key
regulators of pluripotency that are conserved with humans, making them an ideal experimental system to
discover novel regulatory paradigms that induce vertebrate pluripotency. This proposal has three primary
goals. First, the regulatory logic underlying the specificity of embryonic gene activation will be deciphered.
Maternal pluripotency factors act on a transcriptionally quiescent embryonic genome to initially activate only a
few hundred genes, prior to the activation of thousands of genes hours later. Cutting-edge techniques will be
used to map pluripotency factor binding genome wide, at earlier developmental stages than have previously
been profiled. Binding patterns will be compared in the vicinity of early- versus later activated genes, and
distinguishing properties of their respective gene regulatory sequences will be extracted. Second, novel
regulators of embryonic genome activation will be deduced by integrating multiple sources of genomics data.
These factors will be evaluated using innovative loss-of-function strategies to measure their contributions to
embryonic reprogramming and pluripotency. Third, this proposal will uncover post-transcriptional mechanisms
that regulate the maternal pluripotency factors themselves. Biochemical and genetic approaches will be used
to discover factors that bind maternal mRNA to positively or negatively affect their expression, and in turn exert
precise temporal control over pluripotency induction. Together, these analyses will further elucidate the gene
regulatory logic of the early vertebrate embryo and provide a deeper understanding of how pluripotent
identities are induced.

## Key facts

- **NIH application ID:** 10246506
- **Project number:** 5R35GM137973-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Miler T. S. Lee
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $359,164
- **Award type:** 5
- **Project period:** 2020-08-24 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246506

## Citation

> US National Institutes of Health, RePORTER application 10246506, Transcriptome reprogramming in the early embryo (5R35GM137973-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10246506. Licensed CC0.

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