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Biol Open. 2018 Aug 17;7(8). pii: bio033282. doi: 10.1242/bio.033282.

Mammalian embryo comparison identifies novel pluripotency genes associated with the naïve or primed state.

Author information

1
The Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, Cambridge CB2 0SZ, UK andreia.bernardo@crick.ac.uk.
2
Developmental Biology Department, The Francis Crick Institute, 1 Midland Rd, Kings Cross, London NW1 1AT, UK.
3
UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France.
4
Department of Molecular Biology, Faculty of Science, Radboud University, Radboud Institute for Molecular Life Sciences (RIMLS), 6500 HB Nijmegen, The Netherlands.
5
Center for Molecular and Biomolecular Informatics, Radboud Institute of Molecular Life Sciences, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
6
BioTalentum Ltd, Gödöllő, 2100 Godollo, Hungary.
7
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Groennegaardsvej 7, 1870 Frederiksberg C, Denmark.
8
Avantea, Laboratory of Reproductive Technologies, Cremona, 26100 Cremona, Italy.
9
Department of Physiology, University of Lausanne, CH-1005 Lausanne, Switzerland.
10
The Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, Cambridge CB2 0SZ, UK.
11
BioTalentum Ltd, Gödöllő, 2100 Godollo, Hungary andreia.bernardo@crick.ac.uk.
12
Molecular Animal Biotechnology Laboratory, Szent István University, H-2100 Godollo, Gödöllő, Hungary.
13
Departments of Equine Sciences and Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands.

Abstract

During early mammalian development, transient pools of pluripotent cells emerge that can be immortalised upon stem cell derivation. The pluripotent state, 'naïve' or 'primed', depends on the embryonic stage and derivation conditions used. Here we analyse the temporal gene expression patterns of mouse, cattle and porcine embryos at stages that harbour different types of pluripotent cells. We document conserved and divergent traits in gene expression, and identify predictor genes shared across the species that are associated with pluripotent states in vivo and in vitro Amongst these are the pluripotency-linked genes Klf4 and Lin28b The novel genes discovered include naïve- (Spic, Scpep1 and Gjb5) and primed-associated (Sema6a and Jakmip2) genes as well as naïve to primed transition genes (Dusp6 and Trip6). Both Gjb5 and Dusp6 play a role in pluripotency since their knockdown results in differentiation and downregulation of key pluripotency genes. Our interspecies comparison revealed new insights of pluripotency, pluripotent stem cell identity and a new molecular criterion for distinguishing between pluripotent states in various species, including human.

KEYWORDS:

Dusp6; Gjb5; Naïve; Pluripotency; Primed; Trip6

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