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Generation of functional oocytes from male mice in vitro
Mouse induced pluripotent stem cells derived from differentiated fibroblasts could be converted from male (XY) to female (XX), resulting in cells that could form oocytes and give rise to offspring after fertilization.
- Kenta Murakami
- , Nobuhiko Hamazaki
- & Katsuhiko Hayashi
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Article |
A molecular network of conserved factors keeps ribosomes dormant in the egg
Mass spectrometry and structural studies demonstrate the specific changes in protein composition that accompany the transition of ribosomes in zebrafish and Xenopus eggs from a dormant to an active state during early embryogenesis.
- Friederike Leesch
- , Laura Lorenzo-Orts
- & Andrea Pauli
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Article
| Open AccessInheritance of paternal DNA damage by histone-mediated repair restriction
In Caenorhabditis elegans, paternal exposure to ionizing radiation results in HIS-24 and HPL-1-dependent genome instability phenotypes, causing embryonic lethality in the offspring.
- Siyao Wang
- , David H. Meyer
- & Björn Schumacher
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A male germ-cell-specific ribosome controls male fertility
RibosomeST—a ribosome with a specialized nascent polypeptide exit tunnel—cotranslationally regulates the folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm.
- Huiling Li
- , Yangao Huo
- & Jiahao Sha
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Article
| Open AccessHistone H2B.8 compacts flowering plant sperm through chromatin phase separation
H2B.8 is identified as a histone variant that mediates a newly described mechanism of transcription-compatible chromatin condensation in flowering plant sperm cells.
- Toby Buttress
- , Shengbo He
- & Xiaoqi Feng
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Article
| Open AccessA condensate dynamic instability orchestrates actomyosin cortex activation
A phase portrait study is presented that shows the chemically driven dynamics of short-lived F-actin-rich condensates that support actomyosin cortex formation.
- Victoria Tianjing Yan
- , Arjun Narayanan
- & Stephan W. Grill
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Article
| Open AccessOocytes maintain ROS-free mitochondrial metabolism by suppressing complex I
Oocytes prevent the production of reactive oxygen species by remodelling the mitochondrial electron transport chain through elimination of complex I, a strategy that enables their long-term viability.
- Aida Rodríguez-Nuevo
- , Ariadna Torres-Sanchez
- & Elvan Böke
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Article |
Sex-specific chromatin remodelling safeguards transcription in germ cells
Following global DNA demethylation, mouse gonadal primordial germ cells undergo remodelling of repressive chromatin modifications, resulting in a sex-specific signature that is required to safeguard the transcriptional program.
- Tien-Chi Huang
- , Yi-Fang Wang
- & Petra Hajkova
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Article |
Reconstitution of the oocyte transcriptional network with transcription factors
Eight transcription factors are identified that, when overexpressed, are sufficient to grow oocyte-like cells from mouse pluripotent stem cells.
- Nobuhiko Hamazaki
- , Hirohisa Kyogoku
- & Katsuhiko Hayashi
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Article |
Origin and elaboration of a major evolutionary transition in individuality
Obligate endosymbiosis between the bacteria Blochmannia and ants of the Camponotini tribe originated through co-option of pre-existing molecular capacities and rewiring of developmental gene regulatory networks.
- Ab. Matteen Rafiqi
- , Arjuna Rajakumar
- & Ehab Abouheif
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Article |
SPOCD1 is an essential executor of piRNA-directed de novo DNA methylation
Newly identified protein SPOCD1 is crucial in de novo DNA methylation directed by PIWI proteins and piRNAs, helping to control DNA silencing in mouse male germline.
- Ansgar Zoch
- , Tania Auchynnikava
- & Dónal O’Carroll
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Letter |
Maternal vitamin C regulates reprogramming of DNA methylation and germline development
The effect of vitamin C deprivation on mouse germline development is analysed, revealing that maternal vitamin C is required for proper DNA demethylation and the development of fetal oocytes, whereas the lack of vitamin C during pregnancy leads to reduced female fecundity in the offspring.
- Stephanie P. DiTroia
- , Michelle Percharde
- & Miguel Ramalho-Santos
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Article |
Insect egg size and shape evolve with ecology but not developmental rate
Analyses of insect eggs as well as genetic and life-history traits of insects show that where eggs are laid, rather than universal allometric constants, developmental rate or adult body size, underlies size and shape evolution.
- Samuel H. Church
- , Seth Donoughe
- & Cassandra G. Extavour
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Letter |
Mitochondrial fragmentation drives selective removal of deleterious mtDNA in the germline
An in situ hybridization approach is used to visualize mitochondrial DNA germline selection in Drosophila, revealing the role of mitochondrial fragmentation in the selection against deleterious mutations.
- Toby Lieber
- , Swathi P. Jeedigunta
- & Thomas R. Hurd
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Letter |
Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1
Stella, a factor essential for female fertility, protects the oocyte methylome in mice by suppressing de novo DNA methylation mediated by the DNA methyltransferase DNMT1.
- Yingfeng Li
- , Zhuqiang Zhang
- & Bing Zhu
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Letter |
OTX2 restricts entry to the mouse germline
The transcription factor OTX2 ensures that germline induction is initially kept in check and only proceeds after OTX2 downregulation.
- Jingchao Zhang
- , Man Zhang
- & Ian Chambers
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Article |
Extensive sex differences at the initiation of genetic recombination
Differential DNA methylation and the long-range effects of chromatin organization lead to pronounced differences in recombination landscape between males and females.
- Kevin Brick
- , Sarah Thibault-Sennett
- & Galina V. Petukhova
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Letter |
Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte
Gonadal germline epigenetic reprogramming involves an interplay between DNA methylation, the polycomb complex and Tet1 in both DNA methylation dependent and independent roles, to ensure the activation of a specific subset of genes critical for progression of gametogenesis.
- Peter W. S. Hill
- , Harry G. Leitch
- & Petra Hajkova
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Letter |
A lysosomal switch triggers proteostasis renewal in the immortal C. elegans germ lineage
Sperm-activated lysosomes enhance proteostasis in nematode oocytes just before fertilization; this could prevent transmission of damaged proteins to the next generation and may explain the immortality of the germ-cell lineage.
- K. Adam Bohnert
- & Cynthia Kenyon
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Letter |
Parental influence on human germline de novo mutations in 1,548 trios from Iceland
Whole-genome sequencing data of 14,688 Icelanders, including 1,548 parent–offspring trios, show how the age and sex of parents affect the rate and spectrum of de novo mutations.
- Hákon Jónsson
- , Patrick Sulem
- & Kari Stefansson
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Letter |
Reconstitution in vitro of the entire cycle of the mouse female germ line
Using a protocol that recapitulates both meiosis and oocyte growth in vitro, the authors induce mouse pluripotent stem cells to differentiate into fully functional oocytes that can be fertilized and generate viable offspring, thereby recapitulating the full mammalian female germline cycle in a dish.
- Orie Hikabe
- , Nobuhiko Hamazaki
- & Katsuhiko Hayashi
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Letter |
Sequence-dependent but not sequence-specific piRNA adhesion traps mRNAs to the germ plasm
Maternal mRNAs are tethered within the Drosophila germ plasm via base-pairing interactions between mRNAs and piRNPs containing the Aub Piwi protein; the preference for certain mRNAs to be tethered appears to be related to their longer length, which provides more potential piRNP-binding sites, and the results suggest a new role for piRNAs in germ-cell specification independent of their role in transposon silencing.
- Anastassios Vourekas
- , Panagiotis Alexiou
- & Zissimos Mourelatos
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Letter |
NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers
In mouse embryonic stem cells converted to an epiblast fate in vitro—a state in which the cells can also gain germ cell fate if exposed to the signalling molecule BMP4—the sole expression of the transcription factor NANOG is shown to be sufficient to induce germ cell fate, in the absence of BMP4.
- Kazuhiro Murakami
- , Ufuk Günesdogan
- & M. Azim Surani
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Article |
Juno is the egg Izumo receptor and is essential for mammalian fertilization
The egg receptor for Izumo, a sperm cell-surface protein required for male fertility, is identified here and renamed Juno; these findings show that the Izumo–Juno interaction is conserved within mammals, and open new opportunities for the development of fertility treatments and contraceptives.
- Enrica Bianchi
- , Brendan Doe
- & Gavin J. Wright
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Letter |
Role of Tet1 in erasure of genomic imprinting
This study establishes an important role for the enzyme Tet1 in erasing genomic imprinting in vivo — mice with a knockout of paternal Tet1 give rise to progeny with imprinting defects and associated growth and development defects, which leads to early embryonic lethality; furthermore, analysis of the DNA methylation dynamics in reprogramming primordial germ cells (PGCs) suggests that Tet1 is required at a late stage of the reprogramming process, in the second wave of DNA demethylation in PGCs.
- Shinpei Yamaguchi
- , Li Shen
- & Yi Zhang
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Letter |
HELQ promotes RAD51 paralogue-dependent repair to avert germ cell loss and tumorigenesis
Interstrand crosslink (ICL) repair involves proteins whose mutation results in the disorder Fanconi anaemia: here gene knockdown studies in mice show that the absence of HELQ, a protein previously implicated in ICL repair, compromises germ cell development and results in tumour predisposition due to defective recombination at damaged replication forks.
- Carrie A. Adelman
- , Rafal L. Lolo
- & Simon J. Boulton
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Letter |
PRC1 coordinates timing of sexual differentiation of female primordial germ cells
The Polycomb repressive complex 1 (PRC1) is found to have important gene-dosage-dependent and sex-specific roles in primordial germ cell (PGC) development, including the maintenance of high levels of Oct4 and Nanog and ensuring the proper timing of meiosis through the suppression of retinoic acid signalling in female PGCs.
- Shihori Yokobayashi
- , Ching-Yeu Liang
- & Antoine H. F. M. Peters
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News & Views |
Stem cells bear eggs
Researchers have coaxed cultured embryonic stem cells to develop into eggs that then give rise to normal offspring. The discovery should help to decode the molecular basis of gamete formation and might lead to treatments for infertility.
- Sihem Cheloufi
- & Konrad Hochedlinger
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Letter |
Tet1 controls meiosis by regulating meiotic gene expression
A loss-of-function approach in mice is used to show that the methylcytosine dioxygenase Tet1 has a role in regulating meiosis and meiotic gene activation in female germ cells; Tet1 deficiency does not greatly affect genome-wide demethylation but has a more specific effect on the expression of a subset of meiotic genes.
- Shinpei Yamaguchi
- , Kwonho Hong
- & Yi Zhang
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Research Highlights |
Molecule blocks sperm production
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Letter |
An inverse relationship to germline transcription defines centromeric chromatin in C. elegans
Centromere identity is thought to be epigenetically propagated by stable inheritance of nucleosomes containing the histone variant CENP-A; the authors propose a different model here in which germline transcription defines the genomic regions that exclude CENP-A incorporation during embryogenesis in the holocentric worm Caenorhabditis elegans.
- Reto Gassmann
- , Andreas Rechtsteiner
- & Arshad Desai
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Letter |
The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements
- Serena De Fazio
- , Nenad Bartonicek
- & Dónal O’Carroll
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News & Views |
In vitro sperm maturation
Anticancer therapies can impair male fertility. Whereas men can opt to freeze their sperm before treatment, young boys don't produce mature sperm and so lack this choice. Work in mice offers hope for such patients. See Letter p.504
- Marco Seandel
- & Shahin Rafii
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Letter |
In vitro production of functional sperm in cultured neonatal mouse testes
Reproducing the complex process of spermatogenesis in vitro might lead to the development of new diagnostic and therapeutic techniques for male infertility. This study establishes in vitro organ culture conditions that can support complete spermatogenesis in mice. The in-vitro-derived spermatids and sperm produced healthy and fertile mice, and testis tissue fragments used as a starting material for in vitro spermatogenesis could be cryopreserved for months and then resumed full spermatogenesis in vitro.
- Takuya Sato
- , Kumiko Katagiri
- & Takehiko Ogawa
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Research Highlights |
Molecular evolution: Sperm-making origins