Comparative Transcriptomic Analysis of Embryo Implantation in Mice and Rats

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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Assessment of Embryo-Induced Transcriptomic Changes in Hamster Uterus Using RNA-Seq

Cellular Physiology and Biochemistry ◽

10.1159/000489371 ◽

2018 ◽

Vol 46 (5) ◽

pp. 1868-1878 ◽

Cited By ~ 6

Author(s):

Ming-Yu Huang ◽

Wen-Qian Zhang ◽

Miao Zhao ◽

Can Zhu ◽

Jia-Peng He ◽

...

Keyword(s):

Differentially Expressed Genes ◽

Embryo Implantation ◽

Bioinformatic Analysis ◽

Differentially Expressed ◽

Implantation Site ◽

Rna Seq ◽

Promoter Regions ◽

Functional Clustering ◽

Gene Network Analysis ◽

Transcriptomic Changes

Background/Aims: The mouse is widely used as an animal model for studying human embryo implantation. However, the mouse is unique in that both ovarian progesterone and estrogen are critical to implantation, whereas in the majority of species (e.g. human and hamster) implantation can occur in the presence of progesterone alone. Methods: In this study, we analyzed embryo-induced transcriptomic changes in the hamster uterus during embryo implantation by using RNA-seq. Differentially expressed genes were characterized by bioinformatic analysis. Results: We identified a total of 781 differentially expressed genes, of which 367 genes were up-regulated and 414 genes were down-regulated at the implantation site compared to the inter-implantation site. Functional clustering and gene network analysis highlighted the cell cycle process in uterus upon embryo implantation. By examining of the promoter regions of differentially expressed genes, we identified 7 causal transcription factors. Additionally, through connectivity map (CMap) analysis, multiple compounds were identified to have potential anti-implantation effects due to their ability to reverse embryo-induced transcriptomic changes. Conclusion: Our study provides a valuable resource for in-depth understanding of the mechanism underlying embryo implantation.

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A study on regional differences in decidualization of the mouse uterus

Reproduction ◽

10.1530/rep-16-0486 ◽

2017 ◽

Vol 153 (5) ◽

pp. 645-653 ◽

Cited By ~ 3

Author(s):

Miao Zhao ◽

Wen-Qian Zhang ◽

Ji-Long Liu

Keyword(s):

Differentially Expressed Genes ◽

Regional Differences ◽

Molecular Mechanisms ◽

Cell Metabolism ◽

Gene Expression Pattern ◽

Differentially Expressed ◽

Hub Genes ◽

Promoter Regions ◽

Mouse Uterus ◽

Region Gene

Although regional differences in mouse decidualization have been recognized for decades, the molecular mechanisms remain understudied. In the present study, by using RNA-seq, we compared transcriptomic differences between the anti-mesometrial (AM) region and the mesometrial (M) region of mouse uterus on day 8 of pregnancy. A total of 1423 differentially expressed genes were identified, of which 811 genes were upregulated and 612 genes were downregulated in the AM region compared to those in the M region. Gene ontology analysis showed that upregulated genes were generally involved in cell metabolism and differentiation, whereas downregulated genes were associated with lymphocyte themes and immune response. Through network analysis, we identified a total of 6 hub genes. These hub genes are likely more important than other genes due to their key positions in the network. We also examined the promoter regions of differentially expressed genes for the enrichment of transcription factor-binding sites. In the end, we demonstrated that a similar regional gene expression pattern can be observed in the artificial decidualization model. Our study contributes to an increase in the knowledge on the molecular mechanisms underlying regional decidualization in mice.

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Differentially Expressed miRNAs in Mouse Uterus during Embryo Implantation

Indian Journal of Animal Research ◽

10.18805/ijar.b-1270 ◽

2020 ◽

Author(s):

Dingren Cao ◽

Jingjie Liang ◽

Lijun Liu ◽

Xiaowei Zhang ◽

Shuang Shi ◽

...

Keyword(s):

Posttranscriptional Regulation ◽

Transcriptome Sequencing ◽

Embryo Implantation ◽

Enrichment Analysis ◽

Negative Control ◽

Differentially Expressed ◽

Mouse Uterus ◽

Differentially Expressed Mirnas ◽

Implantation Sites ◽

Sequencing Result

Background: MicroRNAs (miRNAs) play key roles in posttranscriptional regulation during the window of implantation. However, which miRNA may play regulatory role during the window of implantation remains to be studied in depth. This paper aimed to explore the miRNAs that played regulatory roles during the process of implantation. Methods: RNA sequencing was performed to analyze mice uterus tissue in gestation day 1 (D1), gestation day 4 (D4) and gestation day5 (D5). The tissues in D5 were divided into embryo implantation sites (D5IMS) and inter-implantation sites (D5IIS). The differentially expressed miRNAs were screened and bioinformatics analyzed. Transfecting miR-183-5p mimics into HEC-1-A cells, genes regulated by miR-183-5p were analyzed by transcriptome sequencing. Result: Eleven differentially expressed miRNAs were identified during the window of implantation. KEGG enrichment analysis showed that the most differentially expressed miRNAs mainly related to binding and signaling transduction related pathways. Especially miR-183-5p, miR-182-5p, miR-199b-5p and miR-218-5p play a crucial role in regulating many important pathways. Transcriptome sequencing results showed that there were 19 up-regulated and 31 down-regulated genes in the miR-183-5p mimics group compared with the negative control (NC) group. This work laid a foundation for the study of miRNA in early pregnancy.

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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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Differential Morpho-Physiological and Transcriptomic Responses to Heat Stress in Two Blueberry Species

International Journal of Molecular Sciences ◽

10.3390/ijms22052481 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2481

Author(s):

Jodi Callwood ◽

Kalpalatha Melmaiee ◽

Krishnanand P. Kulkarni ◽

Amaranatha R. Vennapusa ◽

Diarra Aicha ◽

...

Keyword(s):

Heat Stress ◽

Molecular Mechanisms ◽

Stomatal Closure ◽

Enrichment Analysis ◽

Leaf Size ◽

Vaccinium Corymbosum ◽

Climatic Conditions ◽

Differentially Expressed ◽

Transcriptomic Changes ◽

Go Terms

Blueberries (Vaccinium spp.) are highly vulnerable to changing climatic conditions, especially increasing temperatures. To gain insight into mechanisms underpinning the response to heat stress, two blueberry species were subjected to heat stress for 6 and 9 h at 45 °C, and leaf samples were used to study the morpho-physiological and transcriptomic changes. As compared with Vaccinium corymbosum, Vaccinium darrowii exhibited thermal stress adaptation features such as small leaf size, parallel leaf orientation, waxy leaf coating, increased stomatal surface area, and stomatal closure. RNAseq analysis yielded ~135 million reads and identified 8305 differentially expressed genes (DEGs) during heat stress against the control samples. In V. corymbosum, 2861 and 4565 genes were differentially expressed at 6 and 9 h of heat stress, whereas in V. darrowii, 2516 and 3072 DEGs were differentially expressed at 6 and 9 h, respectively. Among the pathways, the protein processing in the endoplasmic reticulum (ER) was the highly enriched pathway in both the species: however, certain metabolic, fatty acid, photosynthesis-related, peroxisomal, and circadian rhythm pathways were enriched differently among the species. KEGG enrichment analysis of the DEGs revealed important biosynthesis and metabolic pathways crucial in response to heat stress. The GO terms enriched in both the species under heat stress were similar, but more DEGs were enriched for GO terms in V. darrowii than the V. corymbosum. Together, these results elucidate the differential response of morpho-physiological and molecular mechanisms used by both the blueberry species under heat stress, and help in understanding the complex mechanisms involved in heat stress tolerance.

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Cell–Cell Communication at the Embryo Implantation Site of Mouse Uterus Revealed by Single-Cell Analysis

International Journal of Molecular Sciences ◽

10.3390/ijms22105177 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5177

Author(s):

Yi Yang ◽

Jia-Peng He ◽

Ji-Long Liu

Keyword(s):

Single Cell ◽

Molecular Mechanism ◽

Single Cell Analysis ◽

Embryo Implantation ◽

Cell Communication ◽

Human Reproduction ◽

Mouse Uterus ◽

Implantation Sites ◽

Low Efficiency ◽

Signaling Interactions

As a crucial step for human reproduction, embryo implantation is a low-efficiency process. Despite rapid advances in recent years, the molecular mechanism underlying embryo implantation remains poorly understood. Here, we used the mouse as an animal model and generated a single-cell transcriptomic atlas of embryo implantation sites. By analyzing inter-implantation sites of the uterus as control, we were able to identify global gene expression changes associated with embryo implantation in each cell type. Additionally, we predicted signaling interactions between uterine luminal epithelial cells and mural trophectoderm of blastocysts, which represent the key mechanism of embryo implantation. We also predicted signaling interactions between uterine epithelial-stromal crosstalk at implantation sites, which are crucial for post-implantation development. Our data provide a valuable resource for deciphering the molecular mechanism underlying embryo implantation.

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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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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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