Single cell transcriptome analysis of human, marmoset and mouse embryos reveals common and divergent features of preimplantation development

Author:

Boroviak Thorsten12ORCID,Stirparo Giuliano G.1,Dietmann Sabine1,Hernando-Herraez Irene3,Mohammed Hisham3,Reik Wolf3ORCID,Smith Austin14ORCID,Sasaki Erika5,Nichols Jennifer12ORCID,Bertone Paul1ORCID

Affiliation:

1. Wellcome Trust – Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK

2. Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 3EG, UK

3. Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK

4. Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK

5. Central Institute for Experimental Animals, Department of Applied Developmental Biology, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan

Abstract

ABSTRACT The mouse embryo is the canonical model for mammalian preimplantation development. Recent advances in single cell profiling allow detailed analysis of embryogenesis in other eutherian species, including human, to distinguish conserved from divergent regulatory programs and signalling pathways in the rodent paradigm. Here, we identify and compare transcriptional features of human, marmoset and mouse embryos by single cell RNA-seq. Zygotic genome activation correlates with the presence of polycomb repressive complexes in all three species, while ribosome biogenesis emerges as a predominant attribute in primate embryos, supporting prolonged translation of maternally deposited RNAs. We find that transposable element expression signatures are species, stage and lineage specific. The pluripotency network in the primate epiblast lacks certain regulators that are operative in mouse, but encompasses WNT components and genes associated with trophoblast specification. Sequential activation of GATA6, SOX17 and GATA4 markers of primitive endoderm identity is conserved in primates. Unexpectedly, OTX2 is also associated with primitive endoderm specification in human and non-human primate blastocysts. Our cross-species analysis demarcates both conserved and primate-specific features of preimplantation development, and underscores the molecular adaptability of early mammalian embryogenesis.

Funder

Biotechnology and Biological Sciences Research Council

Medical Research Council

Wellcome Trust

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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