Principles of early human development and germ cell program from observed model systems
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Authors
Kobayashi, T,
Zhang, H,
Tang, WC,
Irie, N,
Withey, S,
Klisch, D,
Sybirna, A,
Dietmann, S,
Contreras, DA,
Webb, R,
Allegrucci, C,
Alberio, R,
Surani, MA,
Publication Date
2017-06-15Journal Title
Nature
ISSN
0028-0836
Publisher
Nature Publishing Group
Volume
546
Pages
416-420
Language
English
Type
Article
This Version
AM
Metadata
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Kobayashi, T., Zhang, H., Tang, W., Irie, N., Withey, S., Klisch, D., Sybirna, A., et al. (2017). Principles of early human development and germ cell program from observed model systems. Nature, 546 416-420. https://doi.org/10.1038/nature22812
Abstract
Human primordial germ cells (hPGCs), the precursors of sperm and eggs, originate during weeks 2–3 of early post-implantation development$^{1}$. Using $\textit{in vitro}$ models of hPGC induction$^{2, 3, 4}$, recent studies have suggested that there are marked mechanistic differences in the specification of human and mouse PGCs$^{5}$. This may be due in part to the divergence in their pluripotency networks and early post-implantation development$^{6, 7, 8}$. As early human embryos are not accessible for direct study, we considered alternatives including porcine embryos that, as in humans, develop as bilaminar embryonic discs. Here we show that porcine PGCs originate from the posterior pre-primitive-streak competent epiblast by sequential upregulation of SOX17 and BLIMP1 in response to WNT and BMP signalling. We use this model together with human and monkey $\textit{in vitro}$ models simulating peri-gastrulation development to show the conserved principles of epiblast development for competency for primordial germ cell fate. This process is followed by initiation of the epigenetic program$^{9, 10, 11}$ and regulated by a balanced $\textit{SOX17–BLIMP1}$ gene dosage. Our combinatorial approach using human, porcine and monkey $\textit{in vivo}$ and $\textit{in vitro}$ models provides synthetic insights into early human development.
Sponsorship
Wellcome Trust
Medical Research Council
BBSRC
Funder references
UNIVERSITY OF NOTTINGHAM (FB BBSRC) (BB/M001466/1)
MRC (MC_PC_12009)
MRC (MR/P009948/1)
Wellcome Trust (096738/Z/11/Z)
Identifiers
External DOI: https://doi.org/10.1038/nature22812
This record's URL: https://www.repository.cam.ac.uk/handle/1810/265821
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