# Characterization of the gene regulatory network governing the first cell fate decision in mammalian embryonic development

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $549,648

## Abstract

PROJECT SUMMARY
Although the “master regulators” that maintain the self-renewal of pluripotent embryonic stem cells and
extraembryonic trophoblast stem cells are relatively well understood, little is known about how these
transcription factors are regulated in vivo at early stages of embryogenesis. Molecular genetics and
embryology studies have identified signaling pathways required to direct cells to become trophoblast or
embryonic epiblast, but the transcription factors that activate expression of pluripotency master regulators
(PMRs) or trophoblast master regulators (TMRs) in each cell remain largely unknown. This major gap in our
understanding of early development is due to at least two factors. First, technical barriers prevent the use of
many molecular and genomics approaches in embryos consisting of low cell numbers. Second, there are
significant discrepancies between the totipotent blastomeres of early embryos (where most PMRs and
TMRs begin to be expressed) and cell culture models of totipotent cells. Therefore, a new approach that
combines comprehensive methods for identification of regulators of PMR and TMR expression with
sensitive new methods of testing their functions in vivo is necessary to fill this major gap in our
understanding of the early embryonic gene regulatory network (GRN). We propose three aims to address
this problem. Aim 1 is focused on comprehensive identification of transcription factors regulating PMRs and
TMRs and uncovering their regulatory functions. Aim 2 will generate a lineage-resolved atlas of epigenetic
changes that occur as cells select either the epiblast or trophoblast fate, as well as identify the direct targets
of transcription factors that participate in cell fate specification. In Aim 3, we propose to dissect the
mechanisms by which developmental transcription factors help elicit these epigenetic changes and
generate a model of the totipotent GRN that mediates this decision. Successful completion of these studies
will reshape our understanding of early embryonic gene regulation, as well as specification of epiblast and
trophoblast cell fate.

## Key facts

- **NIH application ID:** 10364821
- **Project number:** 1R01HD104971-01A1
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Thomas G Fazzio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $549,648
- **Award type:** 1
- **Project period:** 2022-07-12 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364821

## Citation

> US National Institutes of Health, RePORTER application 10364821, Characterization of the gene regulatory network governing the first cell fate decision in mammalian embryonic development (1R01HD104971-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10364821. Licensed CC0.

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