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Cell Rep. 2017 Aug 1;20(5):1215-1228. doi: 10.1016/j.celrep.2017.07.009.

Single-Cell Landscape of Transcriptional Heterogeneity and Cell Fate Decisions during Mouse Early Gastrulation.

Author information

1
Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
2
EMBL-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK; Wellcome Trust Sanger Institute, Single-Cell Genomics Centre, Cambridge CB10 1SA, UK.
3
Wellcome Trust Sanger Institute, Single-Cell Genomics Centre, Cambridge CB10 1SA, UK.
4
Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 3EG, UK.
5
Wellcome Trust Sanger Institute, Single-Cell Genomics Centre, Cambridge CB10 1SA, UK; Department of Human Genetics, Human Genome Laboratory, KU Leuven, 3000 Leuven, Belgium.
6
Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 3EG, UK. Electronic address: jn270@cam.ac.uk.
7
EMBL-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK; Wellcome Trust Sanger Institute, Single-Cell Genomics Centre, Cambridge CB10 1SA, UK; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 ORE, UK. Electronic address: marioni@ebi.ac.uk.
8
Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK; Wellcome Trust Sanger Institute, Single-Cell Genomics Centre, Cambridge CB10 1SA, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK. Electronic address: wolf.reik@babraham.ac.uk.

Abstract

The mouse inner cell mass (ICM) segregates into the epiblast and primitive endoderm (PrE) lineages coincident with implantation of the embryo. The epiblast subsequently undergoes considerable expansion of cell numbers prior to gastrulation. To investigate underlying regulatory principles, we performed systematic single-cell RNA sequencing (seq) of conceptuses from E3.5 to E6.5. The epiblast shows reactivation and subsequent inactivation of the X chromosome, with Zfp57 expression associated with reactivation and inactivation together with other candidate regulators. At E6.5, the transition from epiblast to primitive streak is linked with decreased expression of polycomb subunits, suggesting a key regulatory role. Notably, our analyses suggest elevated transcriptional noise at E3.5 and within the non-committed epiblast at E6.5, coinciding with exit from pluripotency. By contrast, E6.5 primitive streak cells became highly synchronized and exhibit a shortened G1 cell-cycle phase, consistent with accelerated proliferation. Our study systematically charts transcriptional noise and uncovers molecular processes associated with early lineage decisions.

KEYWORDS:

X-chromosome; embryo; epiblast; gastrulation; primitive endoderm; primitive streak; single-cell RNA-seq; transcriptional noise

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PMID:
28768204
PMCID:
PMC5554778
DOI:
10.1016/j.celrep.2017.07.009
[Indexed for MEDLINE]
Free PMC Article

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