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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2016 (publ. 2015, arch)     Display Documents



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ID: 717258.0, MPI für molekulare Biomedizin / Jahrbuch 2016 (publ. 2015, arch)
Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile
Authors:Sugawa, F.; Arauzo-Bravo, M. J.; Yoon, J.; Kim, K. P.; Aramaki, S.; Wu, G.; Stehling, M.; Psathaki, O. E.; Hubner, K.; Scholer, H. R.
Date of Publication (YYYY-MM-DD):2015-04-15
Title of Journal:EMBO J
Volume:34
Issue / Number:8
Start Page:1009
End Page:1024
Review Status:Internal review
Audience:Not Specified
Abstract / Description:Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre-migratory PGC-like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm-like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of de novo DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3-6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC-derived gametes for reproductive medicine.
Free Keywords:Activins/pharmacology; Animals; Bone Morphogenetic Protein 4/pharmacology; Cell Differentiation/drug effects/*genetics; Cells, Cultured; Epigenesis, Genetic; Fibroblast Growth Factor 2/pharmacology; Germ Cells/cytology/*physiology; Humans; Mice; Microarray Analysis; Pluripotent Stem Cells/drug effects/*physiology; Repressor Proteins/*genetics; Transcriptome/drug effects; Blimp1; human pluripotent stem cells; primordial germ cell precursors; primordial germ cell specification
External Publication Status:published
Document Type:Article
Communicated by:Keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Munster, Germany Group of Computational Biology and Bioinformatics, Biodonostia Health Research Institute, San Sebastian, Spain IKERBASQUE, Basque Foundation for Science, Bilbao, Spain. Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Munster, Germany Medical Faculty, University of Munster, Munster, Germany office@mpi-muenster.mpg.de.
Identifiers:ISSN:1460-2075 (Electronic) 0261-4189 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/25750208 [ID No:2]
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