scholarly journals Use of proteomics to identify highly abundant maternal factors that drive the egg-to-embryo transition

Reproduction ◽  
2010 ◽  
Vol 139 (5) ◽  
pp. 809-823 ◽  
Author(s):  
Piraye Yurttas ◽  
Eric Morency ◽  
Scott A Coonrod
Keyword(s):  
Maternal Effect ◽  
Transcriptional Profiling ◽  
Human Reproduction ◽  
Transcriptional Level ◽  
Peptidylarginine Deiminase ◽  
Mammalian Oocyte ◽  
Accurate Picture ◽  
Maternal Effect Genes ◽  
Microarray Studies ◽  
Storage Structures

As IVF becomes an increasingly popular method for human reproduction, it is more critical than ever to understand the unique molecular composition of the mammalian oocyte. DNA microarray studies have successfully provided valuable information regarding the identity and dynamics of factors at the transcriptional level. However, the oocyte transcribes and stores a large amount of material that plays no obvious role in oogenesis, but instead is required to regulate embryogenesis. Therefore, an accurate picture of the functional state of the oocyte requires both transcriptional profiling and proteomics. Here, we summarize our previous studies of the oocyte proteome, and present new panels of oocyte proteins that we recently identified in screens of metaphase II-arrested mouse oocytes. Importantly, our studies indicate that several abundant oocyte proteins are not, as one might predict, ubiquitous housekeeping proteins, but instead are unique to the oocyte. Furthermore, mouse studies indicate that a number of these factors arise from maternal effect genes (MEGs). One of the identified MEG proteins, peptidylarginine deiminase 6, localizes to and is required for the formation of a poorly characterized, highly abundant cytoplasmic structure: the oocyte cytoplasmic lattices. Additionally, a number of other MEG-derived abundant proteins identified in our proteomic screens have been found by others to localize to another unique oocyte feature: the subcortical maternal complex. Based on these observations, we put forth the hypothesis that the mammalian oocyte contains several unique storage structures, which we have named maternal effect structures, that facilitate the oocyte-to-embryo transition.

scholarly journals A merged microarray meta-dataset for transcriptionally profiling colorectal neoplasm formation and progression

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Michael Rohr ◽  
Jordan Beardsley ◽  
Sai Preethi Nakkina ◽  
Xiang Zhu ◽  
Jihad Aljabban ◽  
...  
Keyword(s):  
Empirical Bayes ◽  
Transcriptional Profiling ◽  
Gene Expression Omnibus ◽  
Bayes Estimation ◽  
Transcriptional Level ◽  
Neoplastic Progression ◽  
Tissue Samples ◽  
Molecular Events ◽  
Cross Platform ◽  
Microarray Studies

AbstractTranscriptional profiling of pre- and post-malignant colorectal cancer (CRC) lesions enable temporal monitoring of molecular events underlying neoplastic progression. However, the most widely used transcriptomic dataset for CRC, TCGA-COAD, is devoid of adenoma samples, which increases reliance on an assortment of disparate microarray studies and hinders consensus building. To address this, we developed a microarray meta-dataset comprising 231 healthy, 132 adenoma, and 342 CRC tissue samples from twelve independent studies. Utilizing a stringent analytic framework, select datasets were downloaded from the Gene Expression Omnibus, normalized by frozen robust multiarray averaging and subsequently merged. Batch effects were then identified and removed by empirical Bayes estimation (ComBat). Finally, the meta-dataset was filtered for low variant probes, enabling downstream differential expression as well as quantitative and functional validation through cross-platform correlation and enrichment analyses, respectively. Overall, our meta-dataset provides a robust tool for investigating colorectal adenoma formation and malignant transformation at the transcriptional level with a pipeline that is modular and readily adaptable for similar analyses in other cancer types.

scholarly journals Variants in Maternal Effect Genes and Relaxed Imprinting Control in a Special Placental Mesenchymal Dysplasia Case with Mild Trophoblast Hyperplasia

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 544
Author(s):  
Tien-Chi Huang ◽  
Kung-Chao Chang ◽  
Jen-Yun Chang ◽  
Yi-Shan Tsai ◽  
Yao-Jong Yang ◽  
...  
Keyword(s):  
Maternal Effect ◽  
Hydatidiform Mole ◽  
Placental Tissue ◽  
Differentially Methylated Region ◽  
Normal Birth ◽  
Maternal Effect Genes ◽  
Common Etiology ◽  
Artificial Abortion ◽  
Secondary Dmr ◽  
Placental Mesenchymal Dysplasia

Placental mesenchymal dysplasia (PMD) and partial hydatidiform mole (PHM) placentas share similar characteristics, such as placental overgrowth and grape-like placental tissues. Distinguishing PMD from PHM is critical because the former can result in normal birth, while the latter diagnosis will lead to artificial abortion. Aneuploidy and altered dosage of imprinted gene expression are implicated in the pathogenesis of PHM and also some of the PMD cases. Diandric triploidy is the main cause of PHM, whereas mosaic diploid androgenetic cells in the placental tissue have been associated with the formation of PMD. Here, we report a very special PMD case also presenting with trophoblast hyperplasia phenotype, which is a hallmark of PHM. This PMD placenta has a normal biparental diploid karyotype and is functionally sufficient to support normal fetal growth. We took advantage of this unique case to further dissected the potential common etiology between these two diseases. We show that the differentially methylated region (DMR) at NESP55, a secondary DMR residing in the GNAS locus, is significantly hypermethylated in the PMD placenta. Furthermore, we found heterozygous mutations in NLRP2 and homozygous variants in NLRP7 in the mother’s genome. NLRP2 and NLRP7 are known maternal effect genes, and their mutation in pregnant females affects fetal development. The variants/mutations in both genes have been associated with imprinting defects in mole formation and potentially contributed to the mild abnormal imprinting observed in this case. Finally, we identified heterozygous mutations in the X-linked ATRX gene, a known maternal–zygotic imprinting regulator in the patient. Overall, our study demonstrates that PMD and PHM may share overlapping etiologies with the defective/relaxed dosage control of imprinted genes, representing two extreme ends of a spectrum.

Septic shock and systemic inflammatory response syndrome patients' CD15+ granulocytes were subjected to global transcriptional profiling (SIRS)

2021 ◽  
Author(s):  
Marni Mack ◽  
Argo Easston
Keyword(s):  
Gene Expression ◽  
United States ◽  
Septic Shock ◽  
Immune Cells ◽  
Transcriptional Profiling ◽  
The United States ◽  
Transcriptional Level ◽  
Data Set ◽  
Transcriptional Alterations ◽  
Level I

In the United States, sepsis, the body's response to infection in a typically sterile circulation, is a leading causeof death (1). To assess the primary transcriptional alterations associated with each illness state, I utilized amicroarray data set from a cohort of thirtyone individuals with septic shock or systemic inflammatory responsesyndrome (2). At the transcriptional level, I discovered that the granulocytes of patients with SIRS weresimilar to those of patients with septic shock. SIRS showed a “intermediate” gene expression state betweenthat of control patients and that of septic shock patients for numerous genes expressed in the granulocyte. Thediscovery of the most differentially expressed genes in the granulocytic immune cells of patients with septicshock might aid the development of new therapies or diagnostics for an illness with a 14.7 percent to 29.9% inhospitaldeath rate despite decades of study (1).

scholarly journals Transcriptional and post-transcriptional regulation and transcriptional memory of chromatin regulators in response to low temperature

2019 ◽  
Author(s):  
K. Vyse ◽  
L. Faivre ◽  
M. Romich ◽  
M. Pagter ◽  
D. Schubert ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Low Temperature ◽  
Transcriptional Activation ◽  
Large Scale ◽  
Transcriptional Profiling ◽  
Large Fraction ◽  
Histone Variants ◽  
Transcriptional Level ◽  
Large Set ◽  
Dynamic Regulation

AbstractChromatin regulation ensures stable repression of stress-inducible genes under non-stress conditions and transcriptional activation and memory of such an activation of those genes when plants are exposed to stress. However, there is only limited knowledge on how chromatin genes are regulated at the transcriptional and post-transcriptional level upon stress exposure and relief from stress. We have therefore set-up a RT-qPCR-based platform for high-throughput transcriptional profiling of a large set of chromatin genes. We find that the expression of a large fraction of these genes is regulated by cold. In addition, we reveal an induction of several DNA and histone demethylase genes and certain histone variants after plants have been shifted back to ambient temperature (deacclimation), suggesting a role in the memory of cold acclimation. We also re-analyse large scale transcriptomic datasets for transcriptional regulation and alternative splicing (AS) of chromatin genes, uncovering an unexpected level of regulation of these genes, particularly at the splicing level. This includes several vernalization regulating genes whose AS results in cold-regulated protein diversity. Overall, we provide a profiling platform for the analysis of chromatin regulatory genes and integrative analyses of their regulation, suggesting a dynamic regulation of key chromatin genes in response to low temperature stress.

scholarly journals A transgenic system for targeted ablation of reproductive and maternal-effect genes

Development ◽  
2021 ◽  
Vol 148 (12) ◽  
Author(s):  
Sylvain Bertho ◽  
Odelya Kaufman ◽  
KathyAnn Lee ◽  
Adrian Santos-Ledo ◽  
Daniel Dellal ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Maternal Effect ◽  
Early Embryo ◽  
Gene Products ◽  
Reverse Genetic ◽  
Genetic Screens ◽  
Maternal Effect Genes ◽  
Forward Genetic Screens ◽  
Embryonic Life ◽  
Bucky Ball

ABSTRACT Maternally provided gene products regulate the earliest events of embryonic life, including formation of the oocyte that will develop into an egg, and eventually into an embryo. Forward genetic screens have provided invaluable insights into the molecular regulation of embryonic development, including the essential contributions of some genes whose products must be provided to the transcriptionally silent early embryo for normal embryogenesis, called maternal-effect genes. However, other maternal-effect genes are not accessible due to their essential zygotic functions during embryonic development. Identifying these regulators is essential to fill the large gaps in our understanding of the mechanisms and molecular pathways contributing to fertility and to maternally regulated developmental processes. To identify these maternal factors, it is necessary to bypass the earlier requirement for these genes so that their potential later functions can be investigated. Here, we report reverse genetic systems to identify genes with essential roles in zebrafish reproductive and maternal-effect processes. As proof of principle and to assess the efficiency and robustness of mutagenesis, we used these transgenic systems to disrupt two genes with known maternal-effect functions: kif5ba and bucky ball.

scholarly journals Identification of maternal-effect genes in zebrafish using maternal crispants

Development ◽  
2021 ◽  
Author(s):  
Cara E. Moravec ◽  
Gabriella C. Voit ◽  
Jarred Otterlee ◽  
Francisco Pelegri
Keyword(s):  
Maternal Effect ◽  
Reverse Genetics ◽  
Germ Line ◽  
Maternal Factors ◽  
Single Generation ◽  
Maternal Effect Genes ◽  
Biallelic Mutations ◽  
Genome Activation

In animals, early development is dependent on a pool of maternal factors, both RNA and proteins, which are required for basic cellular process and cell differentiation until zygotic genome activation. The role of a majority of these maternally expressed factors is not fully understood. By exploiting the biallelic editing ability of CRISPR-Cas9, we identify and characterize maternal-effect genes in a single generation, using a maternal crispant technique. We validated the ability to generate biallelic mutations in the germline by creating maternal crispants that phenocopied previously characterized maternal-effect genes: motley/birc5b, tmi/prc1l, and aura/mid1ip1. Additionally, by targeting maternally expressed genes of unknown function in zebrafish, we identified two new maternal-effect zebrafish genes, kpna7 and fhdc3. The genetic identity of these maternal crispants was confirmed by sequencing haploid progeny from F0 females, which allowed the analysis of newly induced lesions in the maternal germ line. Our studies show that maternal crispants allow for the effective identification and primary characterization of maternal-effect genes in a single generation, facilitating the reverse genetics analysis of maternal factors that drive embryonic development.

scholarly journals A Transgenic System for Targeted Ablation of Reproductive and Maternal-Effect genes

2020 ◽  
Author(s):  
Sylvain Bertho ◽  
Odelya Kaufman ◽  
KathyAnn Lee ◽  
Adrian Santos-Ledo ◽  
Daniel Dellal ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Maternal Effect ◽  
Early Embryo ◽  
Reverse Genetic ◽  
Genetic Screens ◽  
Maternal Effect Genes ◽  
Genetic Systems ◽  
Forward Genetic Screens ◽  
Embryonic Life ◽  
Summary Statement

AbstractMaternally provided gene products regulate the earliest events of embryonic life, including formation of the oocyte that will develop into an egg, and eventually an embryo. Forward genetic screens have provided invaluable insights into the molecular regulation of embryonic development, including essential contributions of some genes whose products must be provided to the transcriptionally silent early embryo for normal embryogenesis, maternal-effect genes. However, other maternal-effect genes are not accessible due to their essential zygotic functions during embryonic development. Identifying these regulators is essential to fill the large gaps in our understanding of the mechanisms and molecular pathways contributing to fertility and maternally regulated developmental processes. To identify these maternal factors, it is necessary to bypass the earlier requirement for these genes so that their potential later functions can be investigated. Here we report reverse genetic systems to identify genes with essential roles in reproductive and maternal-effect processes, as proof of principal and to assess the efficiency and robustness of mutagenesis we used these transgenic systems to disrupt two genes with known maternal-effect functions, kif5Ba and bucky ball.Summary StatementWe report reverse genetic systems to identify essential regulators of reproductive and maternal-effect processes, as proof of principal we used these transgenic systems to disrupt genes with known maternal-effect functions.

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