A systems approach toward human primordial germ cell differentiation
NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development
About This Grant
PROJECT SUMMARY Differentiation of human primordial germ cells (hPGCs) from human pluripotent stem cells is the first step toward in vitro gametogenesis, which would enable mechanistic studies and treatment of infertility due to loss of gametes. The mechanisms of hPGC differentiation are poorly understood. As a result, current protocols produce heterogeneous mixtures of hPGC-like cells (hPGCLCs) and other cell types. Our long-term goal is to obtain a systems-level understanding of the signaling and gene regulatory network that control primordial germ cell differentiation in vitro and use this to improve directed differentiation of hPGCLCs for potential therapeutic purposes. The objective of this proposal is to quantitatively determine cell signaling requirements of hPGCLC differentiation with unprecedented spatial and temporal resolution. The central hypothesis is that heterogeneous differentiation and maturation of hPGCLCs is due to heterogeneous cell signaling activity. The rationale is that if we identify what distinguishes more mature hPGCLCs from less mature ones and other cell types that arise at the same time, we can understand defects in their differentiation in vivo and in vitro and create better hPGCLCs. Our hypothesis will be tested through two specific aims: 1) Determine the combinatorial signaling dynamics responsible for hPGCLC induction by single cell tracking of signaling and fate markers in live cells combined with highly multiplexed immunofluorescence. 2) Determine if there are distinct phases of induction and maintenance and elucidate the signaling logic and gene regulatory network that controls hPGCLC maintenance and maturation. Our approach is conceptually innovative by testing if a unique history of signaling determines hPGCLC fate, by accounting for the interplay between exogenous and endogenous signaling in vitro, and by delineating clearly distinct phases of differentiation that start with induction. More generally we are breaking new ground by taking a systems-level approach to human germ line biology that tests hypotheses rigorously and quantitatively by representing them as mathematical models. The proposed work is also experimentally innovative as we use substrate micropatterning to achieve reproducible hPGCLC differentiation and are the first lab to establish long-term high throughput tracking of differentiating pluripotent stem cells as well as the first to adapt multiplexed immunofluorescence to stem cell models of early development. The expected outcome of our work is better fundamental understanding of human germ line differentiation and improved methods to produce hPGCLCs for research of in vitro gametogenesis.
Grant Summary
A systems approach toward human primordial germ cell differentiation is a NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development grant providing up to $391K for university, nonprofit, healthcare org. Applications are due 2031-02-28 (open). Check eligibility and apply with FindGrants.
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Eligibility
How to Apply
Up to $391K
2031-02-28
- 1Confirm your organization is eligible for A systems approach toward human primordial germ cell differentiation from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development before the deadline.
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A systems approach toward human primordial germ cell differentiation: Frequently Asked Questions
Who is eligible for the A systems approach toward human primordial germ cell differentiation?
A systems approach toward human primordial germ cell differentiation is offered by NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the A systems approach toward human primordial germ cell differentiation provide?
A systems approach toward human primordial germ cell differentiation provides up to $391K per award from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the A systems approach toward human primordial germ cell differentiation deadline?
Applications for A systems approach toward human primordial germ cell differentiation are due 2031-02-28 (open). Because deadlines can change, verify the date with the funder, NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the A systems approach toward human primordial germ cell differentiation?
To apply for A systems approach toward human primordial germ cell differentiation, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development.