The objective of our Center is to promote scientific excellence in translational science via well-designed studies of human germ cell development, based on a foundation of knowledge in model systems, and culminating with applications that address critical clinical need. To accomplish our objective, we propose three projects, a pilot project, and four cores. We also present several opportunities for a translational pilot project. The projects are: Project I) Germ Cell Differentiation from Human iPSCs and hESCs (Reijo Pera);Project 2) Translational Regulation of Meiotic Cell Cycle Onset and Progression in the Male (Fuller);Project 3) Derivation of Mature Human Oocytes from Primordial Follicles (Hsueh);and Pilot Project) Regulation of Translational Control in the Oocyte to Embryo Transition (Yao). We also present a translational pilot project for future consideration on primary ovarian insufficiency. Supporting the research are four cores: A) Administration;B) Outreach and Education;C) Microanalysis, Sequencing and Informatics;D) Reproductive Database. This application is a culmination of our reorganization and planning over the last several years and presents our vision for Reproductive and Stem Cell Biology based on outstanding basic and translational science. The application is put forth by a collaborative team that shares common interests in terms of genes and germ cell differentiation and maturation, pathways, developmental systems and overall educational, outreach and research goals. Each project consists of a strong basic component;in addition, three of the five projects and pilots have an equally-strong clinical component encompassing genetic analysis of human germ cell development from pluripotent stem cells to probe fundamental aspects and potential therapies, deriving mature oocytes to remedy primary ovarian insufficiency, and establishing the first registry of women with POI. Each project is relevant to the health of infertile women and men and each is informed by the elegant genetic systems of Drosophila and the mouse. The central theme of our Center is novel, forward-looking and built on a firm foundation of scientific and clinical inquiry with an innovative outreach and educational component with hopes of reaching out to other scientists, healthcare professionals.

Public Health Relevance

Our central theme is that human infertility, associated with few or no germ cells (oocytes or sperm) can be understood via translation of studies from model systems to human biology and can be alleviated by applying principle findings to the clinic. By adhering to the principles of our central theme, we will have an increased ability to define the origins and biological consequences of human infertility and may be able to alleviate common barriers to reproduction in infertile men and women, such as production of few germ cells.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD068158-02
Application #
8249005
Study Section
Special Emphasis Panel (ZHD1-DSR-L (32))
Program Officer
De Paolo, Louis V
Project Start
2011-04-01
Project End
2016-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
2
Fiscal Year
2012
Total Cost
$1,699,625
Indirect Cost
$669,560
Name
Stanford University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Durruthy-Durruthy, Jens; Sebastiano, Vittorio; Wossidlo, Mark et al. (2016) The primate-specific noncoding RNA HPAT5 regulates pluripotency during human preimplantation development and nuclear reprogramming. Nat Genet 48:44-52
Ramathal, Cyril; Angulo, Benjamin; Sukhwani, Meena et al. (2015) DDX3Y gene rescue of a Y chromosome AZFa deletion restores germ cell formation and transcriptional programs. Sci Rep 5:15041
Baker, Catherine Craig; Gim, Byung Soo; Fuller, Margaret T (2015) Cell type-specific translational repression of Cyclin B during meiosis in males. Development 142:3394-402
Briggs, Sharon F; Dominguez, Antonia A; Chavez, Shawn L et al. (2015) Single-Cell XIST Expression in Human Preimplantation Embryos and Newly Reprogrammed Female Induced Pluripotent Stem Cells. Stem Cells 33:1771-81
Cheng, Yuan; Feng, Yi; Jansson, Lina et al. (2015) Actin polymerization-enhancing drugs promote ovarian follicle growth mediated by the Hippo signaling effector YAP. FASEB J 29:2423-30
Cheng, Yuan; Kim, Jaehong; Li, Xiao Xiao et al. (2015) Promotion of ovarian follicle growth following mTOR activation: synergistic effects of AKT stimulators. PLoS One 10:e0117769
Hsueh, Aaron J W; Kawamura, Kazuhiro; Cheng, Yuan et al. (2015) Intraovarian control of early folliculogenesis. Endocr Rev 36:1-24
Briggs, Sharon F; Reijo Pera, Renee A (2014) X chromosome inactivation: recent advances and a look forward. Curr Opin Genet Dev 28:78-82
Durruthy-Durruthy, Jens; Briggs, Sharon F; Awe, Jason et al. (2014) Rapid and efficient conversion of integration-free human induced pluripotent stem cells to GMP-grade culture conditions. PLoS One 9:e94231
Durruthy Durruthy, Jens; Ramathal, Cyril; Sukhwani, Meena et al. (2014) Fate of induced pluripotent stem cells following transplantation to murine seminiferous tubules. Hum Mol Genet 23:3071-84

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