# Cellular and Molecular Basis of Human Primordial Germ Cell Specification

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $335,400

## Abstract

Summary
Human germline cells are essential for human reproduction as only these cells are capable of differentiating
into gametes and transmitting DNA from parent to child. The pioneering cells of the human germline begin to
form during prenatal life when a small number of embryonic cells are set aside around the time of embryo
implantation and gastrulation in a process known as human primordial germ cell (hPGC) specification. This
critical event in human germline cell development has a tremendous impact on an individual's future
reproductive health as a failure in hPGC specification causes certain infertility. In this competitive renewal, the
goal is to increase our fundamental knowledge on the cell and molecular basis of hPGC specification. Based
on experimental results in the previous funding period, we aim to use human embryonic stem cells (hESCs)
and human induced pluripotent stem cells (hiPSCs) and the differentiation of hPGC-like cells (hPGCLCs) to
achieve this goal. The overall hypothesis is that non-rodent and human-specific molecular events have
evolved to regulate hPGC specification. Given that the focus of this grant is largely on regions of the genome
that are uniquely human, this project is perfectly suited to the use of human cell-based models. In aim 1, the
hypothesis to be addressed is that TFAP2C-bound human-specific retrotransposons regulate hPGC
specification. In aim 2, the hypothesis to be addressed is that the expression of TFAP2C bound
retrotransposons are regulated by targeted changes to the epigenome during hPGCLC differentiation. In the
third aim, we will evaluate the relationship between TFAP2C and SOX17 in hPGC specification, with the
hypothesis that TFAP2C functions upstream of SOX17 in a lineage primed hPGC progenitor to regulate
specification of hPGCs. In summary, this competitive renewal builds upon success from the first funding
period to contribute essential knowledge on the identification of new loci in the human genome that have
evolved to regulate the specification and identity of hPGCs.

## Key facts

- **NIH application ID:** 10050468
- **Project number:** 2R01HD079546-06A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Amander Clark
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $335,400
- **Award type:** 2
- **Project period:** 2014-12-20 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10050468

## Citation

> US National Institutes of Health, RePORTER application 10050468, Cellular and Molecular Basis of Human Primordial Germ Cell Specification (2R01HD079546-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10050468. Licensed CC0.

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