STELLA modulates transcriptional and endogenous retrovirus programs during maternal-to-zygotic transition
Abstract
The maternal-to-zygotic transition (MZT) marks the period when the embryonic genome is activated and acquires control of development. Maternally inherited factors play a key role in this critical developmental process, which occurs at the 2-cell stage in mice. We investigated the function of the maternally inherited factor STELLA (DPPA3) using single-cell/embryo approaches. We show that loss of maternal STELLA results in widespread transcriptional mis-regulation and a partial failure of MZT. Strikingly, activation of endogenous retroviruses (ERVs) is significantly impaired in Stella maternal/zygotic knockout embryos, which in turn leads to a failure to upregulate chimeric transcripts. Amongst ERVs, MuERV-L activation is particularly affected by the absence of STELLA, and direct in vivo knockdown of MuERV-L impacts the developmental potential of the embryo. We propose that STELLA is involved in ensuring activation of ERVs, which themselves play a potentially key role during early development, either directly or through influencing embryonic gene expression.
Data availability
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DBTMEE: a database of transcriptome in mouse early embryosPublicly available to download from URL.
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2C::tomato ES cells, 2-cell embryos and wild type oocytesPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE33923).
Article and author information
Author details
Funding
Wellcome (96738)
- Yun Huang
- Dang Vinh Do
- Caroline Lee
- Christopher A Penfold
- Jan J Zylicz
- Jamie A Hackett
- M Azim Surani
Wellcome (92096)
- Yun Huang
- Dang Vinh Do
- Caroline Lee
- Christopher A Penfold
- Jan J Zylicz
- Jamie A Hackett
- M Azim Surani
Cancer Research UK (C6946/A14492)
- Yun Huang
- Dang Vinh Do
- Caroline Lee
- Christopher A Penfold
- Jan J Zylicz
- Jamie A Hackett
- M Azim Surani
European Molecular Biology Laboratory
- Jong Kyoung Kim
- John C Marioni
Cancer Research UK
- Jong Kyoung Kim
- John C Marioni
James Baird Fund, University of Cambridge
- Yun Huang
DGIST Start-up Fund of the Ministry of Science, ICT and Future Planning (2017010073)
- Jong Kyoung Kim
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All husbandry and experiments involving mice were authorized by a UK Home Office Project License 80/2637 and carried out in a Home Office-designated facility.
Copyright
© 2017, Huang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Developmental Biology
- Stem Cells and Regenerative Medicine
Niches are often found in specific positions in tissues relative to the stem cells they support. Consistency of niche position suggests that placement is important for niche function. However, the complexity of most niches has precluded a thorough understanding of how their proper placement is established. To address this, we investigated the formation of a genetically tractable niche, the Drosophila Posterior Signaling Center (PSC), the assembly of which had not been previously explored. This niche controls hematopoietic progenitors of the lymph gland (LG). PSC cells were previously shown to be specified laterally in the embryo, but ultimately reside dorsally, at the LG posterior. Here, using live-imaging, we show that PSC cells migrate as a tight collective and associate with multiple tissues during their trajectory to the LG posterior. We find that Slit emanating from two extrinsic sources, visceral mesoderm and cardioblasts, is required for the PSC to remain a collective, and for its attachment to cardioblasts during migration. Without proper Slit-Robo signaling, PSC cells disperse, form aberrant contacts, and ultimately fail to reach their stereotypical position near progenitors. Our work characterizes a novel example of niche formation and identifies an extrinsic signaling relay that controls precise niche positioning.
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- Developmental Biology
- Structural Biology and Molecular Biophysics
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