scholarly journals Time-resolved succession of epigenetic regulation during early mammalian development

2018 ◽  
Author(s):  
Hebing Chen ◽  
Hao Li ◽  
Shuai Jiang ◽  
Xin Huang ◽  
Wanying Li ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Transcriptional Activity ◽  
Mammalian Development ◽  
Lineage Specification ◽  
Cell Stage ◽  
Time Resolved ◽  
Epigenetic Marks ◽  
Early Mammalian Development ◽  
Mammalian Embryonic Development ◽  
Accessible Chromatin

During early mammalian embryonic development, different epigenetic mechanisms undergo dramatic changes; yet how these interconnected epigenetic layers function together to coordinate expression of the genetic code in a spatiotemporal manner remains unknown. Here, we describe a time-resolved study of the hierarchy of epigenetic marks and events, which we used to model transcriptional programs that cannot be understood by investigating steady state. We found that, following fertilization, the re-establishment of accessible chromatin together with transcription factors inherited from oocytes initiates transcription at the 2-cell stage, and then the introduction of active histone modification, H3K4me3, facilitates gene up-regulation at the 4-cell stage, then stabilization of higher-order chromatin structures at the 8-cell stage further enhances transcriptional activity. During the first lineage specification at ICM, transcription activity multifaceted regulation of epigenetic marks. Finally, we quantitatively model the stage succession of different epigenetic marks on transcriptional programs during early embryonic development.

scholarly journals Early mammalian development: from basic research to the clinic

2019 ◽  
Vol 63 (3-4-5) ◽  
pp. 73-75 ◽  
Author(s):  
Aneta Suwińska ◽  
Anna Ajduk
Keyword(s):  
Embryonic Development ◽  
Basic Research ◽  
Embryonic Cell ◽  
Mammalian Development ◽  
Cell Lineages ◽  
Mammalian Embryos ◽  
New Ideas ◽  
Totipotent Cell ◽  
Early Mammalian Development ◽  
Mammalian Embryonic Development

Preimplantation embryonic development lays the foundations for the future individual. Fertilization, cleavage, differentiation of the first embryonic cell lineages and implantation of the embryo into the maternal uterus are absolutely critical for proper embryogenesis. Solving unanswered questions as well as creating new ideas and theories constitute the main axis of the basic research, which is driven by the curiosity of scientists and their desire to explore the unknown. We researchers have been exploring the development of mammalian embryos for decades, searching for the answer to the most fundamental question in the whole area of biology: how a complex organism derives from a single totipotent cell, a zygote. Due to obvious ethical concerns, animals, such as mice and, currently more and more often, cattle, pigs and rabbits, have become useful models for studying human embryonic development. Unprecedented advancement in cell and molecular biology techniques witnessed in the last years allows us to deepen our understanding of mammalian embryonic development.

scholarly journals Dppa2/4 Counteract De Novo Methylation to Establish a Permissive Epigenome for Development

2020 ◽  
Author(s):  
Kristjan H. Gretarsson ◽  
Jamie A. Hackett
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Developmental Competence ◽  
Epigenetic Memory ◽  
Mammalian Development ◽  
Dna Hypomethylation ◽  
Lineage Specification ◽  
Regulatory Pathways ◽  
Genome Wide ◽  
Early Mammalian Development

ABSTRACTEarly mammalian development entails genome-wide epigenome remodeling, including DNA methylation erasure and reacquisition, which facilitates developmental competence. To uncover the mechanisms that orchestrate DNA methylation (DNAme) dynamics, we coupled a single-cell ratiometric DNAme reporter with unbiased CRISPR screening in ESC. We identify key genes and regulatory pathways that drive global DNA hypomethylation, and characterise roles for Cop1 and Dusp6. We also identify Dppa2 and Dppa4 as essential safeguards of focal epigenetic states. In their absence, developmental genes and evolutionary-young LINE1 elements, which DPPA2 specifically binds, lose H3K4me3 and gain ectopic de novo DNA methylation in pluripotent cells. Consequently, lineage-associated genes (and LINE1) acquire a repressive epigenetic memory, which renders them incompetent for activation during future lineage-specification. Dppa2/4 thereby sculpt the pluripotent epigenome by facilitating H3K4me3 and bivalency to counteract de novo methylation; a function co-opted by evolutionary young LINE1 to evade epigenetic decommissioning.

Symmetry Breaking in the Mammalian Embryo

2018 ◽  
Vol 34 (1) ◽  
pp. 405-426 ◽  
Author(s):  
Hui Ting Zhang ◽  
Takashi Hiiragi
Keyword(s):  
Embryonic Development ◽  
Symmetry Breaking ◽  
Mammalian Species ◽  
Continuous Process ◽  
Model System ◽  
The Body ◽  
Self Organization ◽  
Mammalian Development ◽  
Mammalian Embryo ◽  
Early Mammalian Development

We present an overview of symmetry breaking in early mammalian development as a continuous process from compaction to specification of the body axes. While earlier studies have focused on individual symmetry-breaking events, recent advances enable us to explore progressive symmetry breaking during early mammalian development. Although we primarily discuss embryonic development of the mouse, as it is the best-studied mammalian model system to date, we also highlight the shared and distinct aspects between different mammalian species. Finally, we discuss how insights gained from studying mammalian development can be generalized in light of self-organization principles. With this review, we hope to highlight new perspectives in studying symmetry breaking and self-organization in multicellular systems.

scholarly journals Nobiletin enhances the development and quality of bovine embryos in vitro during two key periods of embryonic genome activation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karina Cañón-Beltrán ◽  
Yulia N. Cajas ◽  
Serafín Peréz-Cerezales ◽  
Claudia L. V. Leal ◽  
Ekaitz Agirregoitia ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Mitochondrial Activity ◽  
Bovine Embryos ◽  
Akt Signaling Pathway ◽  
Cell Stage ◽  
Development In Vitro

AbstractIn vitro culture can alter the development and quality of bovine embryos. Therefore, we aimed to evaluate whether nobiletin supplementation during EGA improves embryonic development and blastocyst quality and if it affects PI3K/AKT signaling pathway. In vitro zygotes were cultured in SOF + 5% FCS (Control) or supplemented with 5, 10 or 25 µM nobiletin (Nob5, Nob10, Nob25) or with 0.03% dimethyl-sulfoxide (CDMSO) during minor (2 to 8-cell stage; MNEGA) or major (8 to 16-cell stage; MJEGA) EGA phase. Blastocyst yield on Day 8 was higher in Nob5 (42.7 ± 1.0%) and Nob10 (44.4 ± 1.3%) for MNEGA phase and in Nob10 (61.0 ± 0.8%) for MJEGA phase compared to other groups. Mitochondrial activity was higher and lipid content was reduced in blastocysts produced with nobiletin, irrespective of EGA phase. The mRNA abundance of CDK2, H3-3B, H3-3A, GPX1, NFE2L2 and PPARα transcripts was increased in 8-cells, 16-cells and blastocysts from nobiletin groups. Immunofluorescence analysis revealed immunoreactive proteins for p-AKT forms (Thr308 and Ser473) in bovine blastocysts produced with nobiletin. In conclusion, nobiletin supplementation during EGA has a positive effect on preimplantation bovine embryonic development in vitro and corroborates on the quality improvement of the produced blastocysts which could be modulated by the activation of AKT signaling pathway.

scholarly journals Retinoic acid signaling is critical during the totipotency window in early mammalian development

2021 ◽  
Author(s):  
Ane Iturbide ◽  
Mayra L. Ruiz Tejeda Segura ◽  
Camille Noll ◽  
Kenji Schorpp ◽  
Ina Rothenaigner ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Regulatory Networks ◽  
Es Cells ◽  
Embryonic Stem ◽  
Mammalian Development ◽  
Cell Stage ◽  
Cell Potential ◽  
Cellular Models ◽  
Early Embryos ◽  
Genome Activation

AbstractTotipotent cells hold enormous potential for regenerative medicine. Thus, the development of cellular models recapitulating totipotent-like features is of paramount importance. Cells resembling the totipotent cells of early embryos arise spontaneously in mouse embryonic stem (ES) cell cultures. Such ‘2-cell-like-cells’ (2CLCs) recapitulate 2-cell-stage features and display expanded cell potential. Here, we used 2CLCs to perform a small-molecule screen to identify new pathways regulating the 2-cell-stage program. We identified retinoids as robust inducers of 2CLCs and the retinoic acid (RA)-signaling pathway as a key component of the regulatory circuitry of totipotent cells in embryos. Using single-cell RNA-seq, we reveal the transcriptional dynamics of 2CLC reprogramming and show that ES cells undergo distinct cellular trajectories in response to RA. Importantly, endogenous RA activity in early embryos is essential for zygotic genome activation and developmental progression. Overall, our data shed light on the gene regulatory networks controlling cellular plasticity and the totipotency program.

scholarly journals STAT signaling is active during early mammalian development

1997 ◽  
Vol 208 (2) ◽  
pp. 190-198 ◽  
Author(s):  
Stephen A. Duncan ◽  
Zhong Zhong ◽  
Zilong Wen ◽  
James E. Darnell
Keyword(s):  
Mammalian Development ◽  
Stat Signaling ◽  
Early Mammalian Development

scholarly journals ESCs injected into the 8-cell stage mouse embryo modify pattern of cleavage and cell lineage specification

2016 ◽  
Vol 141 ◽  
pp. 40-50 ◽  
Author(s):  
Monika Humięcka ◽  
Magdalena Krupa ◽  
Maria M. Guzewska ◽  
Marek Maleszewski ◽  
Aneta Suwińska
Keyword(s):  
Mouse Embryo ◽  
Cell Lineage ◽  
Lineage Specification ◽  
Cell Stage
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