The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline

Abstract
Data availability
Article and author information
Metrics

Abstract

The switch from mitosis to meiosis is the key event marking onset of differentiation in the germline stem cell lineage. In Drosophila, the translational repressor Bgcn is required for spermatogonia to stop mitosis and transition to meiotic prophase and the spermatocyte state. Here we show that the mammalian Bgcn ortholog YTHDC2 facilitates a clean switch from mitosis to meiosis in mouse germ cells, revealing a conserved role for YTHDC2 in this critical cell fate transition. YTHDC2-deficient male germ cells enter meiosis but have a mixed identity, maintaining expression of Cyclin A2 and failing to properly express many meiotic markers. Instead of continuing through meiotic prophase, the cells attempt an abnormal mitotic-like division and die. YTHDC2 binds multiple transcripts including Ccna2 and other mitotic transcripts, binds specific piRNA precursors, and interacts with RNA granule components, suggesting that proper progression of germ cells through meiosis is licensed by YTHDC2 through post-transcriptional regulation.

Data availability

The following data sets were generated

1. Bailey AS
2. Batista PJ
3. Gold RS
4. Chen YG
5. de Rooij DG
6. Chang HY
7. Fuller MT
(2017) Regulation of the transition from mitosis to meiosis by the conserved RNA-helicase YTHDC2/BGCN
NCBI Gene Expression Omnibus (accession no: GSE93567).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=ufuryeoobvedrwx&acc=GSE93567

The following previously published data sets were used

(2015) Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline
NCBI Gene Expression Omnibus (accession no: GSE69946).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=ufuryeoobvedrwx&acc=GSE69946
1. Soumillon M
2. Necsulea A
3. Weier M
4. Brawand D
5. Zhang X
6. Gu H
7. Barthès P
8. Kokkinaki M
9. Nef S
10. Gnirke A
11. Dym M
12. de Massy B
13. Mikkelsen TS
14. Kaessmann H
(2013) Cellular source and mechanisms of high transcriptome complexity in the mammalian testis (RNA-Seq cells)
NCBI Gene Expression Omnibus (accession no: GSE43717).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=ufuryeoobvedrwx&acc=GSE43717
(2014) RNA-Seq and RNA Polymerase II ChIP-Seq of mouse spermatogenesis
NCBI Gene Expression Omnibus (accession no: GSE44346).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=ufuryeoobvedrwx&acc=GSE44346

Article and author information

Author details

Alexis S Bailey

Department of Developmental Biology, Stanford University School of Medicine, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Pedro J Batista

Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Rebecca S Gold

Department of Developmental Biology, Stanford University School of Medicine, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Y Grace Chen

Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Dirk G de Rooij

Center for Reproductive Medicine, University of Amsterdam, Amsterdam, Netherlands

Competing interests
The authors declare that no competing interests exist.
Howard Y Chang

Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Margaret T Fuller

Department of Developmental Biology, Stanford University School of Medicine, Stanford, United States

For correspondence
mtfuller@stanford.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-3804-4987

Funding

National Institutes of Health (NIH T32 HD007249)

Alexis S Bailey

Lalor Foundation (Postdoctoral Fellowship)

Alexis S Bailey

National Cancer Institute (Intramural Research Program of the NIH)

Pedro J Batista

National Institutes of Health (NIH R01 HG004361)

Howard Y Chang

Reed-Hodgson Professorship

Margaret T Fuller

National Institutes of Health (NIH P50 HD068158)

Margaret T Fuller

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health (NIH). All of the experiments were approved by the Stanford University Animal Care and Use Committee (IACUC), protocol (#21656).

Human subjects: Human testis sections were obtained from the Fertility Preservation Program of Pittsburgh. Informed consent was obtained and the testicular tissue freezing protocol was approved by the Institutional Review Board of the University of Pittsburgh.

Copyright

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.