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 (P50)
Project #
5P50HD068158-04
Application #
8638808
Study Section
Special Emphasis Panel (ZHD1)
Program Officer
Moss, Stuart B
Project Start
2011-04-01
Project End
2016-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Stanford University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
Stanford
State
CA
Country
United States
Zip Code
94304
Fang, Fang; Angulo, Benjamin; Xia, Ninuo et al. (2018) A PAX5-OCT4-PRDM1 developmental switch specifies human primordial germ cells. Nat Cell Biol 20:655-665
Bailey, Alexis S; Batista, Pedro J; Gold, Rebecca S et al. (2017) The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline. Elife 6:
Feng, Yi; Zhu, Shoujun; Antaris, Alexander L et al. (2017) Live imaging of follicle stimulating hormone receptors in gonads and bones using near infrared II fluorophore. Chem Sci 8:3703-3711
Fan, Qianlan; Cheng, Yuan; Chang, Hsun-Ming et al. (2017) Sphingosine-1-phosphate promotes ovarian cancer cell proliferation by disrupting Hippo signaling. Oncotarget 8:27166-27176
Feng, Yi; Cui, Peng; Lu, Xiaowei et al. (2017) CLARITY reveals dynamics of ovarian follicular architecture and vasculature in three-dimensions. Sci Rep 7:44810
Panula, Sarita; Reda, Ahmed; Stukenborg, Jan-Bernd et al. (2016) Over Expression of NANOS3 and DAZL in Human Embryonic Stem Cells. PLoS One 11:e0165268
Kawamura, Kazuhiro; Kawamura, Nanami; Hsueh, Aaron J W (2016) Activation of dormant follicles: a new treatment for premature ovarian failure? Curr Opin Obstet Gynecol 28:217-22
Durruthy-Durruthy, Jens; Wossidlo, Mark; Pai, Sunil et al. (2016) Spatiotemporal Reconstruction of the Human Blastocyst by Single-Cell Gene-Expression Analysis Informs Induction of Naive Pluripotency. Dev Cell 38:100-15
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
Zhai, Jun; Yao, Guidong; Dong, Fangli et al. (2016) In Vitro Activation of Follicles and Fresh Tissue Auto-transplantation in Primary Ovarian Insufficiency Patients. J Clin Endocrinol Metab 101:4405-4412

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