Mammalian embryo comparison identifies novel pluripotency genes associated with the naïve or primed state
Andreia S. Bernardo,
Alice Jouneau,
Hendrik Marks,
Philip Kensche,
Julianna Kobolak,
Kristine Freude,
Vanessa Hall,
Anita Feher,
Zsuzsanna Polgar,
Chiara Sartori,
Istvan Bock,
Claire Louet,
Tiago Faial,
Hindrik H. D. Kerstens,
Camille Bouissou,
Gregory Parsonage,
Kaveh Mashayekhi,
James C. Smith,
Giovanna Lazzari,
Poul Hyttel,
Hendrik G. Stunnenberg,
Martijn Huynen,
Roger A. Pedersen,
Andras Dinnyes
Affiliations
Andreia S. Bernardo
The Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, Cambridge CB2 0SZ, UK
Alice Jouneau
UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France
Hendrik Marks
Department of Molecular Biology, Faculty of Science, Radboud University, Radboud Institute for Molecular Life Sciences (RIMLS), 6500 HB Nijmegen, The Netherlands
Philip Kensche
Center for Molecular and Biomolecular Informatics, Radboud Institute of Molecular Life Sciences, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Julianna Kobolak
BioTalentum Ltd, Gödöllő, 2100 Godollo, Hungary
Kristine Freude
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Groennegaardsvej 7, 1870 Frederiksberg C, Denmark
Vanessa Hall
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Groennegaardsvej 7, 1870 Frederiksberg C, Denmark
Anita Feher
BioTalentum Ltd, Gödöllő, 2100 Godollo, Hungary
Zsuzsanna Polgar
BioTalentum Ltd, Gödöllő, 2100 Godollo, Hungary
Chiara Sartori
Avantea, Laboratory of Reproductive Technologies, Cremona, 26100 Cremona, Italy
Istvan Bock
BioTalentum Ltd, Gödöllő, 2100 Godollo, Hungary
Claire Louet
UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy en Josas, France
Tiago Faial
The Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, Cambridge CB2 0SZ, UK
Hindrik H. D. Kerstens
Department of Molecular Biology, Faculty of Science, Radboud University, Radboud Institute for Molecular Life Sciences (RIMLS), 6500 HB Nijmegen, The Netherlands
Camille Bouissou
Developmental Biology Department, The Francis Crick Institute, 1 Midland Rd, Kings Cross, London NW1 1AT, UK
Gregory Parsonage
The Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, Cambridge CB2 0SZ, UK
Kaveh Mashayekhi
BioTalentum Ltd, Gödöllő, 2100 Godollo, Hungary
James C. Smith
Developmental Biology Department, The Francis Crick Institute, 1 Midland Rd, Kings Cross, London NW1 1AT, UK
Giovanna Lazzari
Avantea, Laboratory of Reproductive Technologies, Cremona, 26100 Cremona, Italy
Poul Hyttel
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Groennegaardsvej 7, 1870 Frederiksberg C, Denmark
Hendrik G. Stunnenberg
Department of Molecular Biology, Faculty of Science, Radboud University, Radboud Institute for Molecular Life Sciences (RIMLS), 6500 HB Nijmegen, The Netherlands
Martijn Huynen
Center for Molecular and Biomolecular Informatics, Radboud Institute of Molecular Life Sciences, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Roger A. Pedersen
The Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, Cambridge CB2 0SZ, UK
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.
