Geno-transcriptomic dissection of proteinuria in the uninephrectomized rat uncovers a molecular complexity with sexual dimorphism

Investigation of proteinuria, whose pathophysiology remains incompletely understood, is confounded by differences in the phenotype between males and females. We initiated a sex-specific geno-transcriptomic dissection of proteinuria in uninephrectomized male and female Sabra rats that spontaneously develop focal and segmental glomerulosclerosis, testing the hypothesis that different mechanisms might underlie the pathophysiology of proteinuria between the sexes. In the genomic arm, we scanned the genome of 136 male and 111 female uninephrectomized F2 populations derived from crosses between SBH/y and SBN/y. In males, we identified proteinuria-related quantitative trait loci (QTLs) on RNO2 and 20 and protective QTLs on RNO6 and 9. In females, we detected proteinuria-related QTLs on RNO11, 13, and 20. The only QTL overlap between the sexes was on RNO20. Using consomic strains, we confirmed the functional significance of this QTL in both sexes. In the transcriptomic arm, we searched on a genomewide scale for genes that were differentially expressed in kidneys of SBH/y and SBN/y with and without uninephrectomy. These studies identified within each sex differentially expressed genes of relevance to proteinuria. Integrating genomics with transcriptomics, we identified differentially expressed genes that mapped within the boundaries of the proteinuria-related QTLs, singling out 24 transcripts in males and 30 in females, only 4 of which ( Tubb5, Ubd, Psmb8, and C2) were common to both sexes. Data mining revealed that these transcripts are involved in multiple molecular mechanisms, including immunity, inflammation, apoptosis, matrix deposition, and protease activity, with no single molecular pathway predominating in either sex. These results suggest that the pathophysiology of proteinuria is highly complex and that some of the underlying mechanisms are shared between the sexes, while others are sex specific and may account for the difference in the proteinuric phenotype between males and females.

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Transcriptome profiling of differentially expressed genes of male and female inflorescences in spinach (Spinacia oleracea L.)

Genome ◽

10.1139/gen-2020-0122 ◽

2021 ◽

Author(s):

Zhiyuan Liu ◽

Haoying Wang ◽

Zhaosheng Xu ◽

Helong Zhang ◽

Guoliang Li ◽

...

Keyword(s):

Sex Determination ◽

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Spinacia Oleracea ◽

Transcriptome Profiling ◽

Vital Role ◽

Differentially Expressed ◽

Rna Seq ◽

Male And Female ◽

Spinacia Oleracea L

Spinach (Spinacia oleracea L.) is commonly considered a dioecious plant with heterogametic (XY) and homogametic (XX) sex chromosomes. The characteristic is also utilized for the production of spinach hybrid seeds. However, the molecular mechanisms of sex determination in spinach are still unclear because of a lack of genomic and transcriptomic information. In this study, RNA-sequencing (RNA-seq) was performed in male and female inflorescences to provide insight into the molecular basis of sex determination in spinach. Comparative transcriptome analyses showed that 2,278 differentially expressed genes (DEGs) were identified between male and female inflorescences. A high correlation between the RNA-Seq and qRT-PCR validation for DEGs was observed. Among these, 182 DEGs were annotated to transcription factors including the MYB family protein, bHLH family, and MADS family, suggesting these factors might play a vital role in sex determination. Moreover, 26 DEGs related to flower development, including nine ABCE class genes, were detected. Expression analyses of hormone pathways showed that brassinosteroids may be key hormones related to sex determination in spinach. Overall, this study provides a large amount of DEGs related to sexual expression and lays a foundation for unraveling the regulatory mechanism of sex determination in spinach.

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Identification of Differentially Expressed Genes Associated with Papillary Thyroid Carcinoma

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200402085832 ◽

2020 ◽

Vol 23 (6) ◽

pp. 546-553

Author(s):

Hongyuan Cui ◽

Mingwei Zhu ◽

Junhua Zhang ◽

Wenqin Li ◽

Lihui Zou ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Cellular Proliferation ◽

Mrna Level ◽

Thyroid Tissue ◽

Differentially Expressed ◽

Thyroid Tumors ◽

Papillary Thyroid

Objective: Next-generation sequencing (NGS) was performed to identify genes that were differentially expressed between normal thyroid tissue and papillary thyroid carcinoma (PTC). Materials & Methods: Six candidate genes were selected and further confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry in samples from 24 fresh thyroid tumors and adjacent normal tissues. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to investigate signal transduction pathways of the differentially expressed genes. Results: In total, 1690 genes were differentially expressed between samples from patients with PTC and the adjacent normal tissue. Among these, SFRP4, ZNF90, and DCN were the top three upregulated genes, whereas KIRREL3, TRIM36, and GABBR2 were downregulated with the smallest p values. Several pathways were associated with the differentially expressed genes and involved in cellular proliferation, cell migration, and endocrine system tumor progression, which may contribute to the pathogenesis of PTC. Upregulation of SFRP4, ZNF90, and DCN at the mRNA level was further validated with RT-PCR, and DCN expression was further confirmed with immunostaining of PTC samples. Conclusion: These results provide new insights into the molecular mechanisms of PTC. Identification of differentially expressed genes should not only improve the tumor signature for thyroid tumors as a diagnostic biomarker but also reveal potential targets for thyroid tumor treatment.

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Lipidomics profiling of goose granulosa cell model of stearoyl-CoA desaturase function identifies a pattern of lipid droplets associated with follicle development

Cell & Bioscience ◽

10.1186/s13578-021-00604-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xin Yuan ◽

Shenqiang Hu ◽

Liang Li ◽

Chunchun Han ◽

Hehe Liu ◽

...

Keyword(s):

Differentially Expressed Genes ◽

Lipid Droplets ◽

Cell Model ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Follicle Development ◽

Microscopy Analysis ◽

Stearoyl Coa Desaturase ◽

Underlying Mechanisms

Abstract Background Despite their important functions and nearly ubiquitous presence in cells, an understanding of the biology of intracellular lipid droplets (LDs) in goose follicle development remains limited. An integrated study of lipidomic and transcriptomic analyses was performed in a cellular model of stearoyl-CoA desaturase (SCD) function, to determine the effects of intracellular LDs on follicle development in geese. Results Numerous internalized LDs, which were generally spherical in shape, were dispersed throughout the cytoplasm of granulosa cells (GCs), as determined using confocal microscopy analysis, with altered SCD expression affecting LD content. GC lipidomic profiling showed that the majority of the differentially abundant lipid classes were glycerophospholipids, including PA, PC, PE, PG, PI, and PS, and glycerolipids, including DG and TG, which enriched glycerophospholipid, sphingolipid, and glycerolipid metabolisms. Furthermore, transcriptomics identified differentially expressed genes (DEGs), some of which were assigned to lipid-related Gene Ontology slim terms. More DEGs were assigned in the SCD-knockdown group than in the SCD-overexpression group. Integration of the significant differentially expressed genes and lipids based on pathway enrichment analysis identified potentially targetable pathways related to glycerolipid/glycerophospholipid metabolism. Conclusions This study demonstrated the importance of lipids in understanding follicle development, thus providing a potential foundation to decipher the underlying mechanisms of lipid-mediated follicle development.

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Identification of Differentially Expressed Genes in Porcine Ovaries at Proestrus and Estrus Stages Using RNA-Seq Technique

BioMed Research International ◽

10.1155/2018/9150723 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Songbai Yang ◽

Xiaolong Zhou ◽

Yue Pei ◽

Han Wang ◽

Ke He ◽

...

Keyword(s):

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Hormone Secretion ◽

Differentially Expressed ◽

Receptor Interaction ◽

The Novel ◽

Kegg Pathways ◽

Go Enrichment ◽

Single Organism

Estrus is an important factor for the fecundity of sows, and it is involved in ovulation and hormone secretion in ovaries. To better understand the molecular mechanisms of porcine estrus, the expression patterns of ovarian mRNA at proestrus and estrus stages were analyzed using RNA sequencing technology. A total of 2,167 differentially expressed genes (DEGs) were identified (P≤0.05, log2 Ratio≥1), of which 784 were upregulated and 1,383 were downregulated in the estrus compared with the proestrus group. Gene Ontology (GO) enrichment indicated that these DEGs were mainly involved in the cellular process, single-organism process, cell and cell part, and binding and metabolic process. In addition, a pathway analysis showed that these DEGs were significantly enriched in 33 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including cell adhesion molecules, ECM-receptor interaction, and cytokine-cytokine receptor interaction. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) confirmed the differential expression of 10 selected DEGs. Many of the novel candidate genes identified in this study will be valuable for understanding the molecular mechanisms of the sow estrous cycle.

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Comparative Transcriptomic Analysis of Embryo Implantation in Mice and Rats

Cellular Physiology and Biochemistry ◽

10.1159/000494187 ◽

2018 ◽

Vol 50 (2) ◽

pp. 668-678 ◽

Cited By ~ 1

Author(s):

Wen-Qian Zhang ◽

Miao Zhao ◽

Ming-Yu Huang ◽

Ji-Long Liu

Keyword(s):

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Embryo Implantation ◽

Differentially Expressed ◽

Rat Uterus ◽

Mouse Uterus ◽

Pathway Network ◽

Implantation Sites ◽

High Selection ◽

Transcriptomic Changes

Background/Aims: Embryo implantation is an essential process for eutherian pregnancy, but this process varies across eutherians. The genomic mechanisms that led to the emergence and diversification of embryo implantation are largely unknown. Methods: In this study, we analyzed transcriptomic changes during embryo implantation in mice and rats by using RNA-seq. Bioinformatics and evolutionary analyses were performed to characterize implantation-associated genes in these two species. Results: We identified a total of 518 differentially expressed genes in mouse uterus during implantation, of which 253 genes were up-regulated and 265 genes were down-regulated at the implantation sites compared with the inter-implantation sites. In rat uterus, there were 374 differentially expressed genes, of which 284 genes were up-regulated and 90 genes were down-regulated. A cross-species comparison revealed that 92 up-regulated genes and 20 down-regulated genes were shared. The differences and similarities between mice and rats were investigated further at the gene ontology, pathway, network, and causal transcription factor levels. Additionally, we found that embryo implantation might have evolved through the recruitment of ancient genes into uterine expression. The evolutionary rates of the differentially expressed genes in mouse and rat uterus were significantly lower than those of the non-changed genes, indicating that implantation-related genes are evolutionary conserved due to high selection pressure. Conclusion: Our study provides insights into the molecular mechanisms involved in the evolution of embryo implantation.

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A comparative analysis of differentially expressed mRNAs, miRNAs and circRNAs provides insights into the key genes involved in the high-altitude adaptation of yaks

BMC Genomics ◽

10.1186/s12864-021-08044-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Qianyun Ge ◽

Yongbo Guo ◽

Wangshan Zheng ◽

Yuan Cai ◽

Xuebin Qi ◽

...

Keyword(s):

High Altitude ◽

Molecular Mechanisms ◽

Regulation Of Gene Expression ◽

Differentially Expressed ◽

The Tibetan Plateau ◽

The Core ◽

Processing Pathways ◽

Genetic Information Processing ◽

Altitude Adaptation ◽

The Difference

Abstract Background Yaks that inhabit the Tibetan Plateau exhibit striking phenotypic and physiological differences from cattle and have adapted well to the extreme conditions on the plateau. However, the mechanisms used by these animals for the regulation of gene expression at high altitude are not fully understood. Results Here, we sequenced nine lung transcriptomes of yaks at altitudes of 3400, 4200 and 5000 m, and low-altitude Zaosheng cattle, which is a closely related species, served as controls. The analysis identified 21,764 mRNAs, 1377 circRNAs and 1209 miRNAs. By comparing yaks and cattle, 4975 mRNAs, 252 circRNAs and 75 miRNAs were identified differentially expressed. By comparing yaks at different altitudes, we identified 756 mRNAs, 64 circRNAs and 83 miRNAs that were differentially expressed (fold change ≥2 and P-value < 0.05). The pathways enriched in the mRNAs, circRNAs and miRNAs identified from the comparison of yaks and cattle were mainly associated with metabolism, including ‘glycosaminoglycan degradation’, ‘pentose and glucuronate interconversions’ and ‘flavone and flavonol biosynthesis’, and the mRNAs, circRNAs and miRNAs identified from the comparison of yaks at different altitude gradients were significantly enriched in metabolic pathways and immune and genetic information processing pathways. The core RNAs were identified from the mRNA-miRNA-circRNA networks constructed using the predominant differentially expressed RNAs. The core genes specific to the difference between yaks and cattle were associated with the endoplasmic reticulum and fat deposition, but those identified from the comparison among yaks at different altitude gradients were associated with maintenance of the normal biological functions of cells. Conclusions This study enhances our understanding of the molecular mechanisms involved in hypoxic adaptation in yaks and might contribute to improvements in the understanding and prevention of hypoxia-related diseases.

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Bioinformatics analysis of differentially expressed genes and identification of an miRNA–mRNA network associated with entorhinal cortex and hippocampus in Alzheimer’s disease

Hereditas ◽

10.1186/s41065-021-00190-0 ◽

2021 ◽

Vol 158 (1) ◽

Author(s):

Haoming Li ◽

Linqing Zou ◽

Jinhong Shi ◽

Xiao Han

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Differentially Expressed Genes ◽

Entorhinal Cortex ◽

Molecular Mechanisms ◽

Kegg Pathway ◽

Neurodegenerative Disorder ◽

Early Stage ◽

Differentially Expressed ◽

Hub Genes

Abstract Background Alzheimer’s disease (AD) is a fatal neurodegenerative disorder, and the lesions originate in the entorhinal cortex (EC) and hippocampus (HIP) at the early stage of AD progression. Gaining insight into the molecular mechanisms underlying AD is critical for the diagnosis and treatment of this disorder. Recent discoveries have uncovered the essential roles of microRNAs (miRNAs) in aging and have identified the potential of miRNAs serving as biomarkers in AD diagnosis. Methods We sought to apply bioinformatics tools to investigate microarray profiles and characterize differentially expressed genes (DEGs) in both EC and HIP and identify specific candidate genes and pathways that might be implicated in AD for further analysis. Furthermore, we considered that DEGs might be dysregulated by miRNAs. Therefore, we investigated patients with AD and healthy controls by studying the gene profiling of their brain and blood samples to identify AD-related DEGs, differentially expressed miRNAs (DEmiRNAs), along with gene ontology (GO) analysis, KEGG pathway analysis, and construction of an AD-specific miRNA–mRNA interaction network. Results Our analysis identified 10 key hub genes in the EC and HIP of patients with AD, and these hub genes were focused on energy metabolism, suggesting that metabolic dyshomeostasis contributed to the progression of the early AD pathology. Moreover, after the construction of an miRNA–mRNA network, we identified 9 blood-related DEmiRNAs, which regulated 10 target genes in the KEGG pathway. Conclusions Our findings indicated these DEmiRNAs having the potential to act as diagnostic biomarkers at an early stage of AD.

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Bioinformatic analysis identifies potentially key differentially expressed genes in oncogenesis and progression of clear cell renal cell carcinoma

PeerJ ◽

10.7717/peerj.8096 ◽

2019 ◽

Vol 7 ◽

pp. e8096 ◽

Cited By ~ 2

Author(s):

Haiping Zhang ◽

Jian Zou ◽

Ying Yin ◽

Bo Zhang ◽

Yaling Hu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Differentially Expressed Genes ◽

Renal Cell ◽

Molecular Mechanisms ◽

Clear Cell ◽

Clinical Stage ◽

Stage I ◽

Differentially Expressed ◽

Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is one of the most common and lethal types of cancer within the urinary system. Great efforts have been made to elucidate the pathogeny. However, the molecular mechanism of ccRCC is still not well understood. The aim of this study is to identify key genes in the carcinogenesis and progression of ccRCC. The mRNA microarray dataset GSE53757 was downloaded from the Gene Expression Omnibus database. The GSE53757 dataset contains tumor and matched paracancerous specimens from 72 ccRCC patients with clinical stage I to IV. The linear model of microarray data (limma) package in R language was used to identify differentially expressed genes (DEGs). The protein–protein interaction (PPI) network of the DEGs was constructed using the search tool for the retrieval of interacting genes (STRING). Subsequently, we visualized molecular interaction networks by Cytoscape software and analyzed modules with MCODE. A total of 1,284, 1,416, 1,610 and 1,185 up-regulated genes, and 932, 1,236, 1,006 and 929 down-regulated genes were identified from clinical stage I to IV ccRCC patients, respectively. The overlapping DEGs among the four clinical stages contain 870 up-regulated and 645 down-regulated genes. The enrichment analysis of DEGs in the top module was carried out with DAVID. The results showed the DEGs of the top module were mainly enriched in microtubule-based movement, mitotic cytokinesis and mitotic chromosome condensation. Eleven up-regulated genes and one down-regulated gene were identified as hub genes. Survival analysis showed the high expression of CENPE, KIF20A, KIF4A, MELK, NCAPG, NDC80, NUF2, TOP2A, TPX2 and UBE2C, and low expression of ACADM gene could be involved in the carcinogenesis, invasion or recurrence of ccRCC. Literature retrieval results showed the hub gene NDC80, CENPE and ACADM might be novel targets for the diagnosis, clinical treatment and prognosis of ccRCC. In conclusion, the findings of present study may help us understand the molecular mechanisms underlying the carcinogenesis and progression of ccRCC, and provide potential diagnostic, therapeutic and prognostic biomarkers.

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Insight into Molecular Profile Changes after Skeletal Muscle Contusion Using Microarray and Bioinformatics Analyses

10.21203/rs.3.rs-85830/v1 ◽

2020 ◽

Author(s):

Na Li ◽

Ru-feng Bai ◽

Chun Li ◽

Li-hong Dang ◽

Qiu-xiang Du ◽

...

Keyword(s):

Gene Expression ◽

Network Analysis ◽

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Healing Process ◽

Differentially Expressed ◽

Molecular Profile ◽

Wound Age ◽

Functional Modules

Abstract Background: Muscle trauma frequently occurs in daily life. However, the molecular mechanisms of muscle healing, which partly depend on the extent of the damage, are not well understood. This study aimed to investigate gene expression profiles following mild and severe muscle contusion, and to provide more information about the molecular mechanisms underlying the repair process.Methods: A total of 33 rats were divided randomly into control (n = 3), mild contusion (n = 15), and severe contusion (n = 15) groups; the contusion groups were further divided into five subgroups (1, 3, 24, 48, and 168 h post-injury; n = 3 per subgroup). Then full genome microarray of RNA isolated from muscle tissue was performed to access the gene expression changes during healing process.Results: A total of 2,844 and 2,298 differentially expressed genes were identified in the mild and severe contusion groups, respectively. The analysis of the overlapping differentially expressed genes showed that there are common mechanisms of transcriptomic repair of mild and severe contusion within 48 h post-contusion. This was supported by the results of principal component analysis, hierarchical clustering, and weighted gene co‐expression network analysis of the 1,620 coexpressed genes in mildly and severely contused muscle. From these analyses, we discovered that the gene profiles in functional modules and temporal clusters were similar between the mild and severe contusion groups; moreover, the genes showed time-dependent patterns of expression, which allowed us to identify useful markers of wound age. We then performed an analysis of the functions of genes (including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway annotation, and protein–protein interaction network analysis) in the functional modules and temporal clusters, and the hub genes in each module–cluster pair were identified. Interestingly, we found that genes downregulated within 24−48 h of the healing process were largely associated with metabolic processes, especially oxidative phosphorylation of reduced nicotinamide adenine dinucleotide phosphate, which has been rarely reported. Conclusions: These results improve our understanding of the molecular mechanisms underlying muscle repair, and provide a basis for further studies of wound age estimation.

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Suicide Notes: Exaggerations by Males and Females

Journal of Language and Health ◽

10.37287/jlh.v1i1.94 ◽

2020 ◽

Vol 1 (1) ◽

pp. 1-10

Author(s):

Purbo Kusumastuti ◽

Aulia Apriana ◽

Yazid Basthomi

Keyword(s):

Gender Differences ◽

Gender Stereotypes ◽

Language Production ◽

Positive Emotions ◽

Negative Emotions ◽

Male And Female ◽

Suicide Notes ◽

Males And Females ◽

The Difference ◽

Female Subjects

Touching into the gender differences between males and females in expressing the use of exaggeration expressions, this study analyzes the relevant data using the LIWC tool, the HIP method, and the deficit and difference theories. This study found that in relation to the gender stereotypes, both males and females speak differently, yet also demonstrate similarities. Both the male and female subjects express emotions equally in the language production; yet, the negative emotions are dominated by the males, and the positive emotions are dominated by the females. The difference of emotion productions influences the differences in the males’ production of exaggeration expressions, such as empty adjectives, italic expressions, and hyperbole by the female subjects.

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