Stanford University Center for Reproductive and Stem Cell biology

Summary

Principal Investigator: Margaret T Fuller
Abstract: DESCRIPTION (provided by applicant): 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.
Funding Period: 2011-04-01 - 2016-03-31
more information: NIH RePORT

Top Publications

  1. pmc Role of Survivin in cytokinesis revealed by a separation-of-function allele
    Edith Szafer-Glusman
    Department of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
    Mol Biol Cell 22:3779-90. 2011
  2. pmc Rapid and efficient conversion of integration-free human induced pluripotent stem cells to GMP-grade culture conditions
    Jens Durruthy-Durruthy
    Institute for Stem Cell Biology and Regenerative Medicine, Department of Obstetrics and Gynecology and Department of Genetics, Stanford University, Stanford, California, United States of America
    PLoS ONE 9:e94231. 2014
  3. pmc Fate of induced pluripotent stem cells following transplantation to murine seminiferous tubules
    Jens Durruthy Durruthy
    Department of Genetics and Department of Obstetrics and Gynecology, Institute for Stem Cell Biology and Regenerative Medicine, Center for Reproductive and Stem Cell Biology, Stanford University, Stanford, CA 94305, USA and
    Hum Mol Genet 23:3071-84. 2014
  4. pmc Characterization of the human ESC transcriptome by hybrid sequencing
    Kin Fai Au
    Department of Statistics and Department of Health Research and Policy, Stanford University, Stanford, CA 94305
    Proc Natl Acad Sci U S A 110:E4821-30. 2013
  5. pmc Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment
    Kazuhiro Kawamura
    Department of Obstetrics and Gynecology and Department of Advanced Reproductive Medicine, St Marianna University School of Medicine, Kawasaki, Kanagawa 216 8511, Japan
    Proc Natl Acad Sci U S A 110:17474-9. 2013
  6. pmc Actin cytoskeleton regulates Hippo signaling
    Pradeep Reddy
    Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, United States of America
    PLoS ONE 8:e73763. 2013
  7. ncbi Status of human germ cell differentiation from pluripotent stem cells
    Renee A Reijo Pera
    Institute for Stem Cell Biology and Regenerative Medicine, Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305 5463, USA
    Reprod Fertil Dev 25:396-404. 2013
  8. pmc Oocyte-derived R-spondin2 promotes ovarian follicle development
    Yuan Cheng
    Program of Reproductive and Stem Cell Biology, Stanford University School of Medicine, Stanford, CA 94305 5317, USA
    FASEB J 27:2175-84. 2013
  9. ncbi Germ cell differentiation from pluripotent cells
    Jose V Medrano
    Fundación Instituto Valenciano de Infertilidad, Parc Cientific Universitat de Valencia, Paterna, Valencia, Spain
    Semin Reprod Med 31:14-23. 2013
  10. pmc What Drosophila spermatocytes tell us about the mechanisms underlying cytokinesis
    Maria Grazia Giansanti
    Istituto di Biologia e Patologia Molecolari del CNR, Dipartimento di Biologia e Biotecnologie Università Sapienza di Roma, Piazzale A Moro 5, Roma, Italy
    Cytoskeleton (Hoboken) 69:869-81. 2012

Detail Information

Publications15

  1. pmc Role of Survivin in cytokinesis revealed by a separation-of-function allele
    Edith Szafer-Glusman
    Department of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
    Mol Biol Cell 22:3779-90. 2011
    ..Analysis of this "separation-of-function" allele demonstrates the direct role of Survivin and the CPC in cytokinesis and highlights striking differences in regulation of cytokinesis in different cell systems...
  2. pmc Rapid and efficient conversion of integration-free human induced pluripotent stem cells to GMP-grade culture conditions
    Jens Durruthy-Durruthy
    Institute for Stem Cell Biology and Regenerative Medicine, Department of Obstetrics and Gynecology and Department of Genetics, Stanford University, Stanford, California, United States of America
    PLoS ONE 9:e94231. 2014
    ..To our knowledge, as a proof of principle, these are the first integration-free iPSCs lines that were reproducibly generated through synthetic mRNA reprogramming that could be putatively used for clinical purposes. ..
  3. pmc Fate of induced pluripotent stem cells following transplantation to murine seminiferous tubules
    Jens Durruthy Durruthy
    Department of Genetics and Department of Obstetrics and Gynecology, Institute for Stem Cell Biology and Regenerative Medicine, Center for Reproductive and Stem Cell Biology, Stanford University, Stanford, CA 94305, USA and
    Hum Mol Genet 23:3071-84. 2014
    ..Results indicate that mRNA reprogramming in combination with transplantation may contribute to tools for genetic analysis of human germ cell development...
  4. pmc Characterization of the human ESC transcriptome by hybrid sequencing
    Kin Fai Au
    Department of Statistics and Department of Health Research and Policy, Stanford University, Stanford, CA 94305
    Proc Natl Acad Sci U S A 110:E4821-30. 2013
    ..Results suggest that gene identification, even in well-characterized human cell lines and tissues, is likely far from complete. ..
  5. pmc Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment
    Kazuhiro Kawamura
    Department of Obstetrics and Gynecology and Department of Advanced Reproductive Medicine, St Marianna University School of Medicine, Kawasaki, Kanagawa 216 8511, Japan
    Proc Natl Acad Sci U S A 110:17474-9. 2013
    ....
  6. pmc Actin cytoskeleton regulates Hippo signaling
    Pradeep Reddy
    Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, United States of America
    PLoS ONE 8:e73763. 2013
    ..In summary, using an actin-stabilizing drug we show that actin cytoskeleton is one of the upstream regulators of Hippo signaling capable of activating YAP and increasing its downstream CCN growth factors. ..
  7. ncbi Status of human germ cell differentiation from pluripotent stem cells
    Renee A Reijo Pera
    Institute for Stem Cell Biology and Regenerative Medicine, Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305 5463, USA
    Reprod Fertil Dev 25:396-404. 2013
    ..In the present paper, the current status of germ cell development from stem cells is reviewed in light of potential utility for basic science and clinical applications...
  8. pmc Oocyte-derived R-spondin2 promotes ovarian follicle development
    Yuan Cheng
    Program of Reproductive and Stem Cell Biology, Stanford University School of Medicine, Stanford, CA 94305 5317, USA
    FASEB J 27:2175-84. 2013
    ....
  9. ncbi Germ cell differentiation from pluripotent cells
    Jose V Medrano
    Fundación Instituto Valenciano de Infertilidad, Parc Cientific Universitat de Valencia, Paterna, Valencia, Spain
    Semin Reprod Med 31:14-23. 2013
    ..We review the state of the art in germline differentiation from pluripotent stem cells...
  10. pmc What Drosophila spermatocytes tell us about the mechanisms underlying cytokinesis
    Maria Grazia Giansanti
    Istituto di Biologia e Patologia Molecolari del CNR, Dipartimento di Biologia e Biotecnologie Università Sapienza di Roma, Piazzale A Moro 5, Roma, Italy
    Cytoskeleton (Hoboken) 69:869-81. 2012
    ..Finally, cell type-specific differences in the events that set up and complete cytokinesis are emerging from comparison of spermatocytes with cells undergoing mitosis either elsewhere in the organism or in tissue culture...
  11. pmc C-type natriuretic peptide stimulates ovarian follicle development
    Yorino Sato
    Program of Reproductive and Stem Cell Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305 5317, USA
    Mol Endocrinol 26:1158-66. 2012
    ..Thus, CNP secreted by growing follicles is capable of stimulating preantral and antral follicle growth. In place of FSH, CNP treatment could provide an alternative therapy for female infertility...
  12. pmc Ovarian Kaleidoscope database: ten years and beyond
    Aaron J Hsueh
    Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305 5317, USA
    Biol Reprod 86:192. 2012
    ..In the coming years, we will continue to add new features to serve the ovarian research community...
  13. pmc Intraovarian thrombin and activated protein C signaling system regulates steroidogenesis during the periovulatory period
    Yuan Cheng
    Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305 5317, USA
    Mol Endocrinol 26:331-40. 2012
    ..In addition to assessing the role of thrombin and associated genes in progesterone production by the periovulatory ovary, these findings provide a model with which to study molecular mechanisms underlying thrombin-APC-PAR1/4 signaling...
  14. pmc Divergent RNA-binding proteins, DAZL and VASA, induce meiotic progression in human germ cells derived in vitro
    Jose V Medrano
    Institute for Stem Cell Biology and Regenerative Medicine, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford University, Palo Alto, CA, USA
    Stem Cells 30:441-51. 2012
    ..These studies describe an in vitro model for exploring specifics of human meiosis, a process that is remarkably susceptible to errors that lead to different infertility-related diseases...
  15. ncbi Fate of iPSCs derived from azoospermic and fertile men following xenotransplantation to murine seminiferous tubules
    Cyril Ramathal
    Institute for Stem Cell Biology and Regenerative Medicine, Departments of Genetics and Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA
    Cell Rep 7:1284-97. 2014
    ..Findings indicate that xenotransplantation of human iPSCs directs germ cell differentiation in a manner dependent on donor genetic status...

Research Grants30

  1. Center for the Study of Reproductive Biology and Women's Health
    Jeffrey W Pollard; Fiscal Year: 2013
    ..He holds several senior administrative appointments in the College of Medicine and is well able to administer the proposed SCCPIR internally and to enable effective interactions with other SCCPIRs. ..
  2. Origins and Biological Consequences of Human Infertility
    Linda C Giudice; Fiscal Year: 2013
    ..abstract_text> ..
  3. Functional Analysis of the Embryonic Epigenome in a Non-rodent Model
    Mark E Westhusin; Fiscal Year: 2013
    ....
  4. Penn Center for Study of Epigenetics in Reproduction
    Marisa S Bartolomei; Fiscal Year: 2013
    ..abstract_text> ..