scholarly journals Genome-wide, Single-Cell DNA Methylomics Reveals Increased Non-CpG Methylation during Human Oocyte Maturation

2017 ◽  
Vol 9 (1) ◽  
pp. 397-407 ◽  
Author(s):  
Bo Yu ◽  
Xiao Dong ◽  
Silvia Gravina ◽  
Önder Kartal ◽  
Timothy Schimmel ◽  
...  
Keyword(s):  
Single Cell ◽  
Oocyte Maturation ◽  
Cpg Methylation ◽  
Human Oocyte ◽  
Genome Wide

scholarly journals Single-cell analysis of transcriptome and DNA methylome in human oocyte maturation

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241698
Author(s):  
Bo Yu ◽  
Naresh Doni Jayavelu ◽  
Stephanie L. Battle ◽  
Jessica C. Mar ◽  
Timothy Schimmel ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Single Cell ◽  
Oocyte Maturation ◽  
Gene Expression Regulation ◽  
Single Cell Analysis ◽  
Reproductive Potential ◽  
Cpg Methylation ◽  
Fertility Treatment ◽  
Human Oocyte

Oocyte maturation is a coordinated process that is tightly linked to reproductive potential. A better understanding of gene regulation during human oocyte maturation will not only answer an important question in biology, but also facilitate the development of in vitro maturation technology as a fertility treatment. We generated single-cell transcriptome and used our previously published single-cell methylome data from human oocytes at different maturation stages to investigate how genes are regulated during oocyte maturation, focusing on the potential regulatory role of non-CpG methylation. DNMT3B, a gene encoding a key non-CpG methylation enzyme, is one of the 1,077 genes upregulated in mature oocytes, which may be at least partially responsible for the increased non-CpG methylation as oocytes mature. Non-CpG differentially methylated regions (DMRs) between mature and immature oocytes have multiple binding motifs for transcription factors, some of which bind with DNMT3B and may be important regulators of oocyte maturation through non-CpG methylation. Over 98% of non-CpG DMRs locate in transposable elements, and these DMRs are correlated with expression changes of the nearby genes. Taken together, this data indicates that global non-CpG hypermethylation during oocyte maturation may play an active role in gene expression regulation, potentially through the interaction with transcription factors.

scholarly journals Single-cell analysis of Non-CG methylation dynamics and gene expression in human oocyte maturation

2019 ◽  
Author(s):  
Bo Yu ◽  
Naresh Doni Jayavelu ◽  
Stephanie L. Battle ◽  
Thomas H. Smith ◽  
Samuel E Zimmerman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Single Cell ◽  
Oocyte Maturation ◽  
Gene Expression Regulation ◽  
Single Cell Analysis ◽  
Reproductive Potential ◽  
Fertility Treatment ◽  
Human Oocyte

ABSTRACTOocyte maturation is a coordinated process that is tightly linked to reproductive potential. A better understanding of gene regulation during human oocyte maturation will not only answer an important question in biology, but also facilitate the development of in vitro maturation technology as a fertility treatment. We generated single-cell transcriptome and use previously published single-cell methylome data from human oocytes at different maturation stages to investigate how genes are regulated during oocyte maturation, focusing on the potential regulatory role of non-CG methylation. DNMT3B, a gene encoding a key non-CG methylation enzyme, is one of the 1000 genes upregulated in mature oocytes, which may be at least partially responsible for the increased non-CG methylation as oocytes mature. Non-CG differentially methylated regions (DMRs) between mature and immature oocytes have multiple binding motifs for transcription factors, some of which bind with DNMT3B and may be important regulators of oocyte maturation through non-CG methylation. Over 98% of non-CG DMRs locate in transposable elements, and these DMRs are correlated with expression changes of the nearby genes. Taken together, this data indicates that global non-CG hypermethylation during oocyte maturation may play an active role in gene expression regulation, potentially through the interaction with transcription factors.

scholarly journals Single-cell transcriptome and cell-specific network analysis reveal the reparative effect of neurotrophin-4 in preantral follicles grown in vitro

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yingchun Guo ◽  
Peigen Chen ◽  
Tingting Li ◽  
Lei Jia ◽  
Yi Zhou ◽  
...  
Keyword(s):  
Network Analysis ◽  
Single Cell ◽  
Fertility Preservation ◽  
Oocyte Maturation ◽  
Human Oocyte ◽  
Preantral Follicle ◽  
Preantral Follicles ◽  
Reparative Effect ◽  
Human And Mouse

Abstract Background In-vitro-grow (IVG) of preantral follicles is essential for female fertility preservation, while practical approach for improvement is far from being explored. Studies have indicated that neurotrophin-4 (NT-4) is preferentially expressed in human preantral follicles and may be crucial to preantral follicle growth. Methods We observed the location and expression of Tropomyosin-related kinase B (TRKB) in human and mouse ovaries with immunofluorescence and Western blot, and the relation between oocyte maturation and NT-4 level in follicular fluid (FF). Mice model was applied to investigate the effect of NT-4 on preantral follicle IVG. Single-cell RNA sequencing of oocyte combined with cell-specific network analysis was conducted to uncover the underlying mechanism of effect. Results We reported the dynamic location of TRKB in human and mouse ovaries, and a positive relationship between human oocyte maturation and NT-4 level in FF. Improving effect of NT-4 was observed on mice preantral follicle IVG, including follicle development and oocyte maturation. Transcriptome analysis showed that the reparative effect of NT-4 on oocyte maturation might be mediated by regulation of PI3K-Akt signaling and subsequent organization of F-actin. Suppression of advanced stimulated complement system in granulosa cells might contribute to the improvement. Cell-specific network analysis revealed NT-4 may recover the inflammation damage induced by abnormal lipid metabolism in IVG. Conclusions Our data suggest that NT-4 is involved in ovarian physiology and may improve the efficiency of preantral follicle IVG for fertility preservation.

scholarly journals High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarah E. Pierce ◽  
Jeffrey M. Granja ◽  
William J. Greenleaf
Keyword(s):  
Transcription Factor ◽  
Single Cell ◽  
Cancer Cells ◽  
High Throughput ◽  
Regulatory Networks ◽  
Temporal Dynamics ◽  
Chromatin Accessibility ◽  
Regulatory Regions ◽  
Factor Binding ◽  
Genome Wide

AbstractChromatin accessibility profiling can identify putative regulatory regions genome wide; however, pooled single-cell methods for assessing the effects of regulatory perturbations on accessibility are limited. Here, we report a modified droplet-based single-cell ATAC-seq protocol for perturbing and evaluating dynamic single-cell epigenetic states. This method (Spear-ATAC) enables simultaneous read-out of chromatin accessibility profiles and integrated sgRNA spacer sequences from thousands of individual cells at once. Spear-ATAC profiling of 104,592 cells representing 414 sgRNA knock-down populations reveals the temporal dynamics of epigenetic responses to regulatory perturbations in cancer cells and the associations between transcription factor binding profiles.

scholarly journals High-resolution single-cell 3D-models of chromatin ensembles during Drosophila embryogenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qiu Sun ◽  
Alan Perez-Rathke ◽  
Daniel M. Czajkowsky ◽  
Zhifeng Shao ◽  
Jie Liang
Keyword(s):  
High Resolution ◽  
Single Cell ◽  
3D Models ◽  
Computational Method ◽  
Midblastula Transition ◽  
Genome Wide ◽  
Large Ensembles ◽  
Chromatin Folding ◽  
Function Relationship ◽  
Relationship Of

AbstractSingle-cell chromatin studies provide insights into how chromatin structure relates to functions of individual cells. However, balancing high-resolution and genome wide-coverage remains challenging. We describe a computational method for the reconstruction of large 3D-ensembles of single-cell (sc) chromatin conformations from population Hi-C that we apply to study embryogenesis in Drosophila. With minimal assumptions of physical properties and without adjustable parameters, our method generates large ensembles of chromatin conformations via deep-sampling. Our method identifies specific interactions, which constitute 5–6% of Hi-C frequencies, but surprisingly are sufficient to drive chromatin folding, giving rise to the observed Hi-C patterns. Modeled sc-chromatins quantify chromatin heterogeneity, revealing significant changes during embryogenesis. Furthermore, >50% of modeled sc-chromatin maintain topologically associating domains (TADs) in early embryos, when no population TADs are perceptible. Domain boundaries become fixated during development, with strong preference at binding-sites of insulator-complexes upon the midblastula transition. Overall, high-resolution 3D-ensembles of sc-chromatin conformations enable further in-depth interpretation of population Hi-C, improving understanding of the structure-function relationship of genome organization.

scholarly journals Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns

2021 ◽  
Author(s):  
Yannik Bollen ◽  
Ellen Stelloo ◽  
Petra van Leenen ◽  
Myrna van den Bos ◽  
Bas Ponsioen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Single Cell ◽  
Temporal Dynamics ◽  
De Novo ◽  
Tumor Evolution ◽  
Genome Wide ◽  
Aneuploid Tumor ◽  
Evolutionary Paths ◽  
Tumor Biopsies ◽  
Punctuated Evolution

AbstractCentral to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at single-cell resolution. Here, we present 3D Live-Seq—a protocol that integrates live-cell imaging of tumor organoid outgrowth and whole-genome sequencing of each imaged cell to reconstruct evolving tumor cell karyotypes across consecutive cell generations. Using patient-derived colorectal cancer organoids and fresh tumor biopsies, we demonstrate that karyotype alterations of varying complexity are prevalent and can arise within a few cell generations. Sub-chromosomal acentric fragments were prone to replication and collective missegregation across consecutive cell divisions. In contrast, gross genome-wide karyotype alterations were generated in a single erroneous cell division, providing support that aneuploid tumor genomes can evolve via punctuated evolution. Mapping the temporal dynamics and patterns of karyotype diversification in cancer enables reconstructions of evolutionary paths to malignant fitness.

Changes in histone methylation during human oocyte maturation and IVF- or ICSI-derived embryo development

2010 ◽  
Vol 93 (5) ◽  
pp. 1628-1636 ◽  
Author(s):  
Jie Qiao ◽  
Yuan Chen ◽  
Li-Ying Yan ◽  
Jie Yan ◽  
Ping Liu ◽  
...  
Keyword(s):  
Embryo Development ◽  
Oocyte Maturation ◽  
Histone Methylation ◽  
Human Oocyte

scholarly journals Fine Morphology of Human Oocyte Maturation In Vitro12

1972 ◽  
Vol 7 (3) ◽  
pp. 425-457 ◽  
Author(s):  
L. Zamboni ◽  
R. S. Thompson ◽  
D. Moore Smith
Keyword(s):  
Oocyte Maturation ◽  
Human Oocyte ◽  
Fine Morphology

scholarly journals A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis

2020 ◽  
Author(s):  
Ximena Contreras ◽  
Amarbayasgalan Davaatseren ◽  
Nicole Amberg ◽  
Andi H. Hansen ◽  
Johanna Sonntag ◽  
...  
Keyword(s):  
Single Cell ◽  
Genetic Mosaic ◽  
Genome Wide ◽  
A Genome ◽  
Mosaic Analysis

scholarly journals Intergenerational epigenetic inheritance in reef-building corals

2018 ◽  
Author(s):  
Yi Jin Liew ◽  
Emily J. Howells ◽  
Xin Wang ◽  
Craig T. Michell ◽  
John A. Burt ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Intergenerational Transmission ◽  
Epigenetic Inheritance ◽  
Cpg Methylation ◽  
Epigenetic Mechanisms ◽  
Transgenerational Inheritance ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Hypermethylated Genes

MainThe notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants1,2and metazoans1,3. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations1–4. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals)4. Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.

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