# Dissection of the transcriptional network of human primordial germ cells

> **NIH NIH R01** · CALIFORNIA POLY STATE U SAN LUIS OBISPO · 2021 · $14,100

## Abstract

PROJECT SUMMARY
Human development begins at fertilization, progresses through a series of cleavage divisions, compaction of
the embryo and formation of the blastocyst; then just prior to or during the early stages of gastrulation, a few
cells are set aside or allocated to become the germ cells of the next generation and pass the DNA of one
generation to the next. Defects in germ cell differentiation are a common cause of human infertility that afflicts
10-15% of couples. However, at least in part due to a lack of models of early human germ cell development,
most of the underlying cellular and molecular correlates of infertility remain unknown. The overall goal of this
project is to fill this knowledge void, at least in part, by dissecting the intrinsic transcriptional network in early
human germ cells. The hypothesis underlying this proposal is that a unique TF network, comprised of human
somatic lineage specifiers in cooperation with pluripotency genes, controls the earliest developmental transition
in germ cell differentiation from pluripotent stem cells to human primordial germ cells (hPGCs) by repressing
somatic gene expression while activating germ cell programs; moreover, we hypothesize that the same
network functions to maintain germ cell identity and promote progression to the spermatogonial stage and
beyond. Our preliminary studies have uncovered a unique transcriptional network in human germ cells that is
regulated by an OCT4-PAX5-PRDM1 circuit. To address our hypothesis, we propose three specific aims to: 1)
Map diagnostic genome-wide localization of TFs in bona fide hPGCs. 2) Dissect cooperativity and epistasis of
the TF network (OCT4, SOX17, T and PAX5) in hPGCs by gain- and loss-of-function analysis. 3) Induce
human germ cells via defined TFs. The study is innovative in terms of the hypothesis, preliminary data and the
combination of tools of stem cell biology, differentiation, human genome editing, genome-wide transcriptional,
epigenetic analysis, and computational biology, that we use to accomplish our overall goal. This project is
significant in that it will increase our knowledge of human germ cell developmental genetics by illuminating the
transcriptional network governing acquisition of cell fate from pluripotency to the germ cell lineage, enable
establishment of a robust genetic system that may parallel that of Drosophila and the mouse in terms of the
ability to examine complex genotypes and phenotypes, and may also contribute substantially to potential novel
strategies in clinical applications in diagnosis and development of novel therapeutics for infertility.

## Key facts

- **NIH application ID:** 10151622
- **Project number:** 5R01HD096026-05
- **Recipient organization:** CALIFORNIA POLY STATE U SAN LUIS OBISPO
- **Principal Investigator:** Renee A Reijo Pera
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $14,100
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151622

## Citation

> US National Institutes of Health, RePORTER application 10151622, Dissection of the transcriptional network of human primordial germ cells (5R01HD096026-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10151622. Licensed CC0.

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