scholarly journals Epigenetic dynamics during preimplantation development

Reproduction ◽  
2015 ◽  
Vol 150 (3) ◽  
pp. R109-R120 ◽  
Author(s):  
Chelsea Marcho ◽  
Wei Cui ◽  
Jesse Mager
Keyword(s):  
Genetic Material ◽  
Cell Types ◽  
Dna Demethylation ◽  
Preimplantation Development ◽  
Human Embryos ◽  
Mammalian Development ◽  
Sequencing Technologies ◽  
Active Dna Demethylation ◽  
Generation Sequencing ◽  
Short Days

Successful mammalian development requires descendants of single-cell zygotes to differentiate into diverse cell types even though they contain the same genetic material. Preimplantation dynamics are first driven by the necessity of reprogramming haploid parental epigenomes to reach a totipotent state. This process requires extensive erasure of epigenetic marks shortly after fertilization. During the few short days after formation of the zygote, epigenetic programs are established and are essential for the first lineage decisions and differentiation. Here we review the current understanding of DNA methylation and histone modification dynamics responsible for these early changes during mammalian preimplantation development. In particular, we highlight insights that have been gained through next-generation sequencing technologies comparing human embryos to other models as well as the recent discoveries of active DNA demethylation mechanisms at play during preimplantation.

scholarly journals Bloody coli: a Gene Cocktail in Escherichia coli O104:H4

mBio ◽  
2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Fernando Baquero ◽  
Raquel Tobes
Keyword(s):  
Escherichia Coli ◽  
Next Generation Sequencing ◽  
Genetic Material ◽  
Next Generation ◽  
Content Type ◽  
Pathogenicity Genes ◽  
Sequencing Technologies ◽  
Population Sizes ◽  
Sequential Acquisition ◽  
Generation Sequencing

ABSTRACT A recent study published in mBio [Y. H. Grad et al., mBio 4(1):e00452-12, 2013] indicates that a rapid introgressive evolution has occurred in Escherichia coli O104:H4 by sequential acquisition of foreign genetic material involving pathogenicity traits. O104 genetic promiscuity cannot be readily explained by high population sizes. However, extensive interactions leading to cumulative assemblies of pathogenicity genes might be assured by small K-strategist populations exploiting particular intestinal niches. Next-generation sequencing technologies will be critical to detect particular “gene cocktails” as potentially pathogenic ensembles and to predict the risk of future outbreaks.

CAR expression in human embryos and hESC illustrates its role in pluripotency and tight junctions

Reproduction ◽  
2014 ◽  
Vol 148 (5) ◽  
pp. 531-544 ◽  
Author(s):  
M Krivega ◽  
M Geens ◽  
H Van de Velde
Keyword(s):  
Outer Layer ◽  
Transmembrane Domain ◽  
Splice Variants ◽  
Embryonic Stem ◽  
Cell Types ◽  
Preimplantation Development ◽  
Coxsackie Virus ◽  
Preimplantation Embryos ◽  
Human Embryos ◽  
Adenovirus Receptor

Coxsackie virus and adenovirus receptor,CXADR(CAR), is present during embryogenesis and is involved in tissue regeneration, cancer and intercellular adhesion. We investigated the expression of CAR in human preimplantation embryos and embryonic stem cells (hESC) to identify its role in early embryogenesis and differentiation. CAR protein was ubiquitously present during preimplantation development. It was localised in the nucleus of uncommitted cells, from the cleavage stage up to the precursor epiblast, and corresponded with the presence of solubleCXADR3/7splice variant. CAR was displayed on the membrane, involving in the formation of tight junction at compaction and blastocyst stages in both outer and inner cells, and CAR corresponded with the full-length CAR-containing transmembrane domain. In trophectodermal cells of hatched blastocysts, CAR was reduced in the membrane and concentrated in the nucleus, which correlated with the switch in RNA expression to theCXADR4/7andCXADR2/7splice variants. The cells in the outer layer of hESC colonies contained CAR on the membrane and all the cells of the colony had CAR in the nucleus, corresponding with the transmembraneCXADRandCXADR4/7. Upon differentiation of hESC into cells representing the three germ layers and trophoblast lineage, the expression ofCXADRwas downregulated. We concluded thatCXADRis differentially expressed during human preimplantation development. We described various CAR expressions: i) solubleCXADRmarking undifferentiated blastomeres; ii) transmembrane CAR related with epithelial-like cell types, such as the trophectoderm (TE) and the outer layer of hESC colonies; and iii) soluble CAR present in TE nuclei after hatching. The functions of these distinct forms remain to be elucidated.

scholarly journals DNA Demethylation Pathways: Recent Insights

2013 ◽  
Vol 5 ◽  
pp. GEG.S12143 ◽  
Author(s):  
Cong-jun Li
Keyword(s):  
Dna Methylation ◽  
Mammalian Cells ◽  
De Novo ◽  
Dna Demethylation ◽  
Epigenetic Mark ◽  
Sequencing Technologies ◽  
Active Dna Demethylation ◽  
Mammalian Genomes ◽  
Genome Context

DNA methylation is a major epigenetic regulatory mechanism for gene expression and cell differentiation. Until recently, it was still unclear how unmethylated regions in mammalian genomes are protected from de novo methylation and whether or not active demethylating activity is involved. Even the role of molecules and the mechanisms underlying the processes of active demethylation itself is blurred. Emerging sequencing technologies have led to recent insights into the dynamic distribution of DNA methylation during development and the role of this epigenetic mark within a distinct genome context, such as the promoters, exons, or imprinted control regions. This review summarizes recent insights on the dynamic nature of DNA methylation and demethylation, as well as the mechanisms regulating active DNA demethylation in mammalian cells, which have been fundamental research interests in the field of epigenomics.

scholarly journals Vitamin C Rescues in vitro Embryonic Development by Correcting Impaired Active DNA Demethylation

2021 ◽  
Vol 9 ◽  
Author(s):  
Meiqiang Chu ◽  
Fusheng Yao ◽  
Guangyin Xi ◽  
Jiajun Yang ◽  
Zhenni Zhang ◽  
...  
Keyword(s):  
Vitamin C ◽  
Critical Role ◽  
Underlying Mechanism ◽  
Dna Demethylation ◽  
Preimplantation Development ◽  
Developmental Potential ◽  
Active Dna Demethylation ◽  
Lineage Differentiation ◽  
First Case

During preimplantation development, a wave of genome-wide DNA demethylation occurs to acquire a hypomethylated genome of the blastocyst. As an essential epigenomic event, postfertilization DNA demethylation is critical to establish full developmental potential. Despite its importance, this process is prone to be disrupted due to environmental perturbations such as manipulation and culture of embryos during in vitro fertilization (IVF), and thus leading to epigenetic errors. However, since the first case of aberrant DNA demethylation reported in IVF embryos, its underlying mechanism remains unclear and the strategy for correcting this error remains unavailable in the past decade. Thus, understanding the mechanism responsible for DNA demethylation defects, may provide a potential approach for preventing or correcting IVF-associated complications. Herein, using mouse and bovine IVF embryos as the model, we reported that ten-eleven translocation (TET)-mediated active DNA demethylation, an important contributor to the postfertilization epigenome reprogramming, was impaired throughout preimplantation development. Focusing on modulation of TET dioxygenases, we found vitamin C and α-ketoglutarate, the well-established important co-factors for stimulating TET enzymatic activity, were synthesized in both embryos and the oviduct during preimplantation development. Accordingly, impaired active DNA demethylation can be corrected by incubation of IVF embryos with vitamin C, and thus improving their lineage differentiation and developmental potential. Together, our data not only provides a promising approach for preventing or correcting IVF-associated epigenetic errors, but also highlights the critical role of small molecules or metabolites from maternal paracrine in finetuning embryonic epigenomic reprogramming during early development.

The Influence of Memory-Aware Computation on Distributed BLAST

2019 ◽  
Vol 14 (2) ◽  
pp. 157-163
Author(s):  
Majid Hajibaba ◽  
Mohsen Sharifi ◽  
Saeid Gorgin
Keyword(s):  
Search Time ◽  
Genomic Research ◽  
Local Alignment ◽  
Negative Effects ◽  
Sequencing Technologies ◽  
Percent Improvement ◽  
Fast Processing ◽  
Search Tool ◽  
Memory Awareness ◽  
Generation Sequencing

Background: One of the pivotal challenges in nowadays genomic research domain is the fast processing of voluminous data such as the ones engendered by high-throughput Next-Generation Sequencing technologies. On the other hand, BLAST (Basic Local Alignment Search Tool), a longestablished and renowned tool in Bioinformatics, has shown to be incredibly slow in this regard. Objective: To improve the performance of BLAST in the processing of voluminous data, we have applied a novel memory-aware technique to BLAST for faster parallel processing of voluminous data. Method: We have used a master-worker model for the processing of voluminous data alongside a memory-aware technique in which the master partitions the whole data in equal chunks, one chunk for each worker, and consequently each worker further splits and formats its allocated data chunk according to the size of its memory. Each worker searches every split data one-by-one through a list of queries. Results: We have chosen a list of queries with different lengths to run insensitive searches in a huge database called UniProtKB/TrEMBL. Our experiments show 20 percent improvement in performance when workers used our proposed memory-aware technique compared to when they were not memory aware. Comparatively, experiments show even higher performance improvement, approximately 50 percent, when we applied our memory-aware technique to mpiBLAST. Conclusion: We have shown that memory-awareness in formatting bulky database, when running BLAST, can improve performance significantly, while preventing unexpected crashes in low-memory environments. Even though distributed computing attempts to mitigate search time by partitioning and distributing database portions, our memory-aware technique alleviates negative effects of page-faults on performance.

scholarly journals The Cellular Choreography of Osteoblast Angiotropism in Bone Development and Homeostasis

2021 ◽  
Vol 22 (14) ◽  
pp. 7253
Author(s):  
Georgiana Neag ◽  
Melissa Finlay ◽  
Amy J. Naylor
Keyword(s):  
Endothelial Cells ◽  
Bone Formation ◽  
Drug Targets ◽  
Bone Development ◽  
Cell Types ◽  
Regulatory Relationship ◽  
Sequencing Technologies ◽  
Resolution Imaging ◽  
Molecular Relationships ◽  
Form Type

Interaction between endothelial cells and osteoblasts is essential for bone development and homeostasis. This process is mediated in large part by osteoblast angiotropism, the migration of osteoblasts alongside blood vessels, which is crucial for the homing of osteoblasts to sites of bone formation during embryogenesis and in mature bones during remodeling and repair. Specialized bone endothelial cells that form “type H” capillaries have emerged as key interaction partners of osteoblasts, regulating osteoblast differentiation and maturation and ensuring their migration towards newly forming trabecular bone areas. Recent revolutions in high-resolution imaging methodologies for bone as well as single cell and RNA sequencing technologies have enabled the identification of some of the signaling pathways and molecular interactions that underpin this regulatory relationship. Similarly, the intercellular cross talk between endothelial cells and entombed osteocytes that is essential for bone formation, repair, and maintenance are beginning to be uncovered. This is a relatively new area of research that has, until recently, been hampered by a lack of appropriate analysis tools. Now that these tools are available, greater understanding of the molecular relationships between these key cell types is expected to facilitate identification of new drug targets for diseases of bone formation and remodeling.

scholarly journals Stability of Imprinting and Differentiation Capacity in Naïve Human Cells Induced by Chemical Inhibition of CDK8 and CDK19

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 876
Author(s):  
Raquel Bernad ◽  
Cian J. Lynch ◽  
Rocio G. Urdinguio ◽  
Camille Stephan-Otto Attolini ◽  
Mario F. Fraga ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Primordial Germ Cell ◽  
Normal Karyotype ◽  
Cell Types ◽  
Dna Demethylation ◽  
Starting State ◽  
Teratoma Formation

Pluripotent stem cells can be stabilized in vitro at different developmental states by the use of specific chemicals and soluble factors. The naïve and primed states are the best characterized pluripotency states. Naïve pluripotent stem cells (PSCs) correspond to the early pre-implantation blastocyst and, in mice, constitute the optimal starting state for subsequent developmental applications. However, the stabilization of human naïve PSCs remains challenging because, after short-term culture, most current methods result in karyotypic abnormalities, aberrant DNA methylation patterns, loss of imprinting and severely compromised developmental potency. We have recently developed a novel method to induce and stabilize naïve human PSCs that consists in the simple addition of a chemical inhibitor for the closely related CDK8 and CDK19 kinases (CDK8/19i). Long-term cultured CDK8/19i-naïve human PSCs preserve their normal karyotype and do not show widespread DNA demethylation. Here, we investigate the long-term stability of allele-specific methylation at imprinted loci and the differentiation potency of CDK8/19i-naïve human PSCs. We report that long-term cultured CDK8/19i-naïve human PSCs retain the imprinting profile of their parental primed cells, and imprints are further retained upon differentiation in the context of teratoma formation. We have also tested the capacity of long-term cultured CDK8/19i-naïve human PSCs to differentiate into primordial germ cell (PGC)-like cells (PGCLCs) and trophoblast stem cells (TSCs), two cell types that are accessible from the naïve state. Interestingly, long-term cultured CDK8/19i-naïve human PSCs differentiated into PGCLCs with a similar efficiency to their primed counterparts. Also, long-term cultured CDK8/19i-naïve human PSCs were able to differentiate into TSCs, a transition that was not possible for primed PSCs. We conclude that inhibition of CDK8/19 stabilizes human PSCs in a functional naïve state that preserves imprinting and potency over long-term culture.

scholarly journals Clinical Implications of Polymicrobial Synergism Effects on Antimicrobial Susceptibility

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 144
Author(s):  
William Little ◽  
Caroline Black ◽  
Allie Clinton Smith
Keyword(s):  
Antimicrobial Susceptibility ◽  
Chronic Wounds ◽  
Clinical Laboratory ◽  
Patient Treatment ◽  
Clinical Implications ◽  
Clinical Environment ◽  
Tolerance Mechanisms ◽  
Sequencing Technologies ◽  
Generation Sequencing ◽  
Polymicrobial Infections

With the development of next generation sequencing technologies in recent years, it has been demonstrated that many human infectious processes, including chronic wounds, cystic fibrosis, and otitis media, are associated with a polymicrobial burden. Research has also demonstrated that polymicrobial infections tend to be associated with treatment failure and worse patient prognoses. Despite the importance of the polymicrobial nature of many infection states, the current clinical standard for determining antimicrobial susceptibility in the clinical laboratory is exclusively performed on unimicrobial suspensions. There is a growing body of research demonstrating that microorganisms in a polymicrobial environment can synergize their activities associated with a variety of outcomes, including changes to their antimicrobial susceptibility through both resistance and tolerance mechanisms. This review highlights the current body of work describing polymicrobial synergism, both inter- and intra-kingdom, impacting antimicrobial susceptibility. Given the importance of polymicrobial synergism in the clinical environment, a new system of determining antimicrobial susceptibility from polymicrobial infections may significantly impact patient treatment and outcomes.

scholarly journals The landscape of alternative polyadenylation in single cells of the developing mouse embryo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vikram Agarwal ◽  
Sereno Lopez-Darwin ◽  
David R. Kelley ◽  
Jay Shendure
Keyword(s):  
Rna Binding ◽  
Developmental Stages ◽  
Single Cells ◽  
Neuronal Cell ◽  
Alternative Polyadenylation ◽  
Cell Types ◽  
Untranslated Regions ◽  
Mammalian Development ◽  
Translation Rate ◽  
Dynamic Landscape

Abstract3′ untranslated regions (3′ UTRs) post-transcriptionally regulate mRNA stability, localization, and translation rate. While 3′-UTR isoforms have been globally quantified in limited cell types using bulk measurements, their differential usage among cell types during mammalian development remains poorly characterized. In this study, we examine a dataset comprising ~2 million nuclei spanning E9.5–E13.5 of mouse embryonic development to quantify transcriptome-wide changes in alternative polyadenylation (APA). We observe a global lengthening of 3′ UTRs across embryonic stages in all cell types, although we detect shorter 3′ UTRs in hematopoietic lineages and longer 3′ UTRs in neuronal cell types within each stage. An analysis of RNA-binding protein (RBP) dynamics identifies ELAV-like family members, which are concomitantly induced in neuronal lineages and developmental stages experiencing 3′-UTR lengthening, as putative regulators of APA. By measuring 3′-UTR isoforms in an expansive single cell dataset, our work provides a transcriptome-wide and organism-wide map of the dynamic landscape of alternative polyadenylation during mammalian organogenesis.

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