scholarly journals Cx3cr1-deficient microglia exhibit a premature aging transcriptome

2019 ◽  
Vol 2 (6) ◽  
pp. e201900453 ◽  
Author(s):  
Stefka Gyoneva ◽  
Raghavendra Hosur ◽  
David Gosselin ◽  
Baohong Zhang ◽  
Zhengyu Ouyang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Immunohistochemical Analysis ◽  
Premature Aging ◽  
Rna Seq ◽  
Active Chromatin ◽  
Chronological Aging ◽  
Transcriptomic Signature ◽  
Immune Related Genes ◽  
Old Mice ◽  
Deficient Mice

CX3CR1, one of the highest expressed genes in microglia in mice and humans, is implicated in numerous microglial functions. However, the molecular mechanisms underlying Cx3cr1 signaling are not well understood. Here, we analyzed transcriptomes of Cx3cr1-deficient microglia under varying conditions by RNA-sequencing (RNA-seq). In 2-mo-old mice, Cx3cr1 deletion resulted in the down-regulation of a subset of immune-related genes, without substantial epigenetic changes in markers of active chromatin. Surprisingly, Cx3cr1-deficient microglia from young mice exhibited a transcriptome consistent with that of aged Cx3cr1-sufficient animals, suggesting a premature aging transcriptomic signature. Immunohistochemical analysis of microglia in young and aged mice revealed that loss of Cx3cr1 modulates microglial morphology in a comparable fashion. Our results suggest that CX3CR1 may regulate microglial function in part by modulating the expression levels of a subset of inflammatory genes during chronological aging, making Cx3cr1-deficient mice useful for studying aged microglia.

scholarly journals Analyses of Avascular Mutants Reveal Unique Transcriptomic Signature of Non-conventional Endothelial Cells

2020 ◽  
Vol 8 ◽  
Author(s):  
Boryeong Pak ◽  
Christopher E. Schmitt ◽  
Woosoung Choi ◽  
Jun-Dae Kim ◽  
Orjin Han ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Lineage Tracing ◽  
Molecular Characteristics ◽  
Lateral Plate Mesoderm ◽  
Rna Seq ◽  
Developmental History ◽  
Lateral Plate ◽  
Developmental Origin ◽  
Transcriptomic Signature

Endothelial cells appear to emerge from diverse progenitors. However, to which extent their developmental origin contributes to define their cellular and molecular characteristics remains largely unknown. Here, we report that a subset of endothelial cells that emerge from the tailbud possess unique molecular characteristics that set them apart from stereotypical lateral plate mesoderm (LPM)-derived endothelial cells. Lineage tracing shows that these tailbud-derived endothelial cells arise at mid-somitogenesis stages, and surprisingly do not require Npas4l or Etsrp function, indicating that they have distinct spatiotemporal origins and are regulated by distinct molecular mechanisms. Microarray and single cell RNA-seq analyses reveal that somitogenesis- and neurogenesis-associated transcripts are over-represented in these tailbud-derived endothelial cells, suggesting that they possess a unique transcriptomic signature. Taken together, our results further reveal the diversity of endothelial cells with respect to their developmental origin and molecular properties, and provide compelling evidence that the molecular characteristics of endothelial cells may reflect their distinct developmental history.

scholarly journals Humic-acid-driven escape from eye parasites revealed by RNA-seq and target-specific metabarcoding

2020 ◽  
Author(s):  
Kristina Noreikiene ◽  
Mikhail Ozerov ◽  
Freed Ahmad ◽  
Toomas Kõiv ◽  
Siim Kahar ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Massively Parallel Sequencing ◽  
Intraspecific Diversity ◽  
Rna Seq ◽  
Human Pathogens ◽  
Clear Water ◽  
Intermediate Hosts ◽  
Humic Lakes ◽  
Immune Related Genes ◽  
Host Parasite

Abstract BackgroundNext generation sequencing (NGS) technologies are extensively used to dissect the molecular mechanisms of host-parasite interactions in human pathogens. However, ecological studies have yet to fully exploit the power of NGS as a rich source for formulating and testing new hypotheses. MethodsWe studied Eurasian perch (Perca fluviatilis) and its eye parasite (Trematoda, Diplostomidae) communities in fourteen lakes that differed in humic content in order to explore host-parasite-environment interactions. We hypothesised that high humic content along with low pH would decrease the abundance of the intermediate hosts (gastropods), thus limiting the occurrence of diplostomid parasites in humic lakes. This hypothesis was initially invoked by whole eye RNA-seq data analysis and subsequently tested using PCR-based detection and a novel targeted metabarcoding approach.ResultsWhole eye transcriptome results revealed over expression of immune-related genes and the presence of eye parasite sequences in RNA-seq data obtained from perch living in clear-water lakes. Both PCR-based and targeted-metabarcoding approach showed that perch from humic lakes were completely free from diplostomid parasites, while the prevalence of eye flukes in clear-water lakes that contain low amounts of humic substances was close to 100%, with the majority of NGS reads assigned to Tylodelphys clavata. ConclusionsHigh intraspecific diversity of T. clavata indicates that massively parallel sequencing of naturally pooled samples represents an efficient and powerful strategy for shedding light on cryptic diversity of eye parasites. Our results demonstrate that perch populations in clear-water lakes experience contrasting eye parasite pressure compared to those from humic lakes, which is reflected by prevalent differences in the expression of immune-related genes in the eye. This study highlights the utility of NGS to discover novel host-parasite-environment interactions and provide unprecedented power to characterize the molecular diversity of cryptic parasites.

scholarly journals Humic-acid-driven escape from eye parasites revealed by RNA-seq and target-specific metabarcoding

2020 ◽  
Author(s):  
Kristina Noreikiene ◽  
Mikhail Ozerov ◽  
Freed Ahmad ◽  
Toomas Kõiv ◽  
Siim Kahar ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Massively Parallel Sequencing ◽  
Intraspecific Diversity ◽  
Rna Seq ◽  
Human Pathogens ◽  
Clear Water ◽  
Intermediate Hosts ◽  
Humic Lakes ◽  
Immune Related Genes ◽  
Host Parasite

Abstract Background: Next generation sequencing (NGS) technologies are extensively used to dissect the molecular mechanisms of host-parasite interactions in human pathogens. However, ecological studies have yet to fully exploit the power of NGS as a rich source for formulating and testing new hypotheses. Methods: We studied Eurasian perch (Perca fluviatilis) and its eye parasite (Trematoda, Diplostomidae) communities in 14 lakes that differed in humic content in order to explore host-parasite-environment interactions. We hypothesised that high humic content along with low pH would decrease the abundance of the intermediate hosts (gastropods), thus limiting the occurrence of diplostomid parasites in humic lakes. This hypothesis was initially invoked by whole eye RNA-seq data analysis and subsequently tested using PCR-based detection and a novel targeted metabarcoding approach.Results: Whole eye transcriptome results revealed overexpression of immune-related genes and the presence of eye parasite sequences in RNA-seq data obtained from perch living in clear-water lakes. Both PCR-based and targeted-metabarcoding approach showed that perch from humic lakes were completely free from diplostomid parasites, while the prevalence of eye flukes in clear-water lakes that contain low amounts of humic substances was close to 100%, with the majority of NGS reads assigned to Tylodelphys clavata. Conclusions: High intraspecific diversity of T. clavata indicates that massively parallel sequencing of naturally pooled samples represents an efficient and powerful strategy for shedding light on cryptic diversity of eye parasites. Our results demonstrate that perch populations in clear-water lakes experience contrasting eye parasite pressure compared to those from humic lakes, which is reflected by prevalent differences in the expression of immune-related genes in the eye. This study highlights the utility of NGS to discover novel host-parasite-environment interactions and provide unprecedented power to characterize the molecular diversity of cryptic parasites.

scholarly journals Humic-acid-driven escape from eye parasites revealed by RNA-seq and target-specific metabarcoding

2020 ◽  
Author(s):  
Kristina Noreikiene ◽  
Mikhail Ozerov ◽  
Freed Ahmad ◽  
Toomas Kõiv ◽  
Siim Kahar ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Massively Parallel Sequencing ◽  
Intraspecific Diversity ◽  
Rna Seq ◽  
Human Pathogens ◽  
Clear Water ◽  
Intermediate Hosts ◽  
Humic Lakes ◽  
Immune Related Genes ◽  
Host Parasite

Abstract Background Next generation sequencing (NGS) technologies are extensively used to dissect the molecular mechanisms of host-parasite interactions in human pathogens. However, ecological studies have yet to fully exploit the power of NGS as a rich source for formulating and testing new hypotheses. Methods We studied Eurasian perch (Perca fluviatilis) and its eye parasite (Trematoda, Diplostomidae) communities in fourteen lakes that differed in humic content in order to explore host-parasite-environment interactions. We hypothesised that high humic content along with low pH would decrease the abundance of the intermediate hosts (gastropods), thus limiting the occurrence of diplostomid parasites in humic lakes. This hypothesis was initially invoked by whole eye RNA-seq data analysis and subsequently tested using PCR-based detection and a novel targeted metabarcoding approach.Results Whole eye transcriptome results revealed over expression of immune-related genes and the presence of eye parasite sequences in RNA-seq data obtained from perch living in clear-water lakes. Both PCR-based and targeted-metabarcoding approach showed that perch from humic lakes were completely free from diplostomid parasites, while the prevalence of eye flukes in clear-water lakes that contain low amounts of humic substances was close to 100%, with the majority of NGS reads assigned to Tylodelphys clavata. Conclusions High intraspecific diversity of T. clavata indicates that massively parallel sequencing of naturally pooled samples represents an efficient and powerful strategy for shedding light on cryptic diversity of eye parasites. Our results demonstrate that perch populations in clear-water lakes experience contrasting eye parasite pressure compared to those from humic lakes, which is reflected by prevalent differences in the expression of immune-related genes in the eye. This study highlights the utility of NGS to discover novel host-parasite-environment interactions and provide unprecedented power to characterize the molecular diversity of cryptic parasites.

Identification of immune-related genes in thymus of breast cancer mouse model exposed to different calorie restriction

2019 ◽  
Vol 44 (5) ◽  
pp. 635-645
Author(s):  
Zehra Omeroglu Ulu ◽  
Salih Ulu ◽  
Soner Dogan ◽  
Bilge Guvenc Tuna ◽  
Nehir Ozdemir Ozgenturk
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Calorie Restriction ◽  
Molecular Mechanisms ◽  
Transcriptional Profiling ◽  
Rna Seq ◽  
Expression Levels ◽  
Thymus Tissue ◽  
Different Types ◽  
Immune Related Genes

Abstract Introduction In the present study, RNA sequencing-mediated transcriptome analysis was performed in order to elucidate the molecular mechanisms of the immune response for different types of calorie restriction (CR) application using MMTV-TGF-α breast cancer mouse model. Methods Animals were applied to three different dietary regiments; ad libitum (AL), chronic calorie restriction (CCR) and intermittent calorie restriction (ICR). Using thymus tissues, 6091 differentially expressed genes (DEGs) were identified in three dietary groups. After clustering of total of 6091 DEGs using Gene Ontology (GO) categories, a total of 400 genes were identified to be involved in immune system process (GO:0002376) GO categories. KEGG pathway and gene co-expression network analysis of these immune-related DEGs were done using String database. The results were confirmed with measuring mRNA expression levels of four selected immune-related DEGs genes (Casp3, Thy1, IL-16 and CD4) using quantitative real-time PCR (qPCR). Results The expression levels of immune-related genes were different in three RNA-seq data. Conclusion The results provide useful information to investigate the immune-related transcriptional profiling in thymus tissue of breast cancer mouse model applied to two different types of CR and to identify the specific functional immune related genes in response to CR during cancer development.

scholarly journals Clinicopathologic features of TDO2 overexpression in renal cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Quoc Thang Pham ◽  
Daiki Taniyama ◽  
Yohei Sekino ◽  
Shintaro Akabane ◽  
Takashi Babasaki ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
In Silico Analysis ◽  
Immunohistochemical Analysis ◽  
Rna Seq ◽  
Anoikis Resistance ◽  
Silico Analysis ◽  
Proliferation And Invasion

Abstract Background Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme catabolizing tryptophan. Several lines of evidence revealed that overexpression of TDO2 is involved in anoikis resistance, spheroid formation, proliferation, and invasion and correlates with poor prognosis in some cancers. The aim of this research was to uncover the expression and biofunction of TDO2 in renal cell carcinoma (RCC). Methods To show the expression of TDO2 in RCC, we performed qRT-PCR and immunohistochemistry in integration with TCGA data analysis. The interaction of TDO2 with PD-L1, CD44, PTEN, and TDO2 expression was evaluated. We explored proliferation, colony formation, and invasion in RCC cells line affected by knockdown of TDO2. Results RNA-Seq and immunohistochemical analysis showed that TDO2 expression was upregulated in RCC tissues and was associated with advanced disease and poor survival of RCC patients. Furthermore, TDO2 was co-expressed with PD-L1 and CD44. In silico analysis and in vitro knockout of PTEN in RCC cell lines revealed the ability of PTEN to regulate the expression of TDO2. Knockdown of TDO2 suppressed the proliferation and invasion of RCC cells. Conclusion Our results suggest that TDO2 might have an important role in disease progression and could be a promising marker for targeted therapy in RCC. (199 words)

scholarly journals Comparative Transcriptome Analysis Reveals Sex-Based Differences during the Development of the Adult Parasitic Wasp Cotesia vestalis (Hymenoptera: Braconidae)

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 896
Author(s):  
Yuenan Zhou ◽  
Pei Yang ◽  
Shuang Xie ◽  
Min Shi ◽  
Jianhua Huang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Adult Development ◽  
Sexual Development ◽  
Molecular Mechanisms ◽  
Parasitic Wasp ◽  
Differentially Expressed Gene ◽  
Regulation Mechanism ◽  
Rna Seq ◽  
Male And Female ◽  
Cotesia Vestalis

The endoparasitic wasp Cotesia vestalis is an important biological agent for controlling the population of Plutella xylostella, a major pest of cruciferous crops worldwide. Though the genome of C. vestalis has recently been reported, molecular mechanisms associated with sexual development have not been comprehensively studied. Here, we combined PacBio Iso-Seq and Illumina RNA-Seq to perform genome-wide profiling of pharate adult and adult development of male and female C. vestalis. Taking advantage of Iso-Seq full-length reads, we identified 14,466 novel transcripts as well as 8770 lncRNAs, with many lncRNAs showing a sex- and stage-specific expression pattern. The differentially expressed gene (DEG) analyses showed 2125 stage-specific and 326 sex-specific expressed genes. We also found that 4819 genes showed 11,856 alternative splicing events through combining the Iso-Seq and RNA-Seq data. The results of comparative analyses showed that most genes were alternatively spliced across developmental stages, and alternative splicing (AS) events were more prevalent in females than in males. Furthermore, we identified six sex-determining genes in this parasitic wasp and verified their sex-specific alternative splicing profiles. Specifically, the characterization of feminizer and doublesex splicing between male and female implies a conserved regulation mechanism of sexual development in parasitic wasps.

scholarly journals Analysis of saponins detoxification genes in Ilyonectria mors-panacis G3B inducing root rot of Panax notoginseng by RNA-Seq

2021 ◽  
Author(s):  
Guohong Zeng ◽  
Jin Li ◽  
Yuxiu Ma ◽  
Qian Pu ◽  
Tian Xiao ◽  
...  
Keyword(s):  
Root Rot ◽  
Molecular Mechanisms ◽  
Management Strategies ◽  
Panax Notoginseng ◽  
Glycoside Hydrolases ◽  
Rna Seq ◽  
Host Interaction ◽  
Excellent Starting Point ◽  
Starting Point ◽  
Genes Encoding

AbstractSaponins are kinds of antifungal compounds produced by Panax notoginseng to resist invasion by pathogens. Ilyonectria mors-panacis G3B was the dominant pathogen inducing root rot of P. notoginseng, and the abilities to detoxify saponins were the key to infect P. notoginseng successfully. To research the molecular mechanisms of detoxifying saponins in I. mors-panacis G3B, we used high-throughput RNA-Seq to identify 557 and 1519 differential expression genes (DEGs) in I. mors-panacis G3B with saponins treatments for 4H (Hours) and 12H (Hours) compared with no saponins treatments, respectively. Among these DEGs, we found 93 genes which were simultaneously highly expressed in I. mors-panacis G3B with saponins treatments for 4H and 12H, they mainly belong to genes encoding transporters, glycoside hydrolases, oxidation–reduction enzymes, transcription factors and so on. In addition, there were 21 putative PHI (Pathogen–Host Interaction) genes out of those 93 up-regulated genes. In this report, we analyzed virulence-associated genes in I. mors-panacis G3B which may be related to detoxifying saponins to infect P. notoginseng successfully. They provided an excellent starting point for in-depth study on pathogenicity of I. mors-panacis G3B and developed appropriate root rot disease management strategies in the future.

scholarly journals Non-Coding RNA Signatures of B-Cell Acute Lymphoblastic Leukemia

2021 ◽  
Vol 22 (5) ◽  
pp. 2683
Author(s):  
Princess D. Rodriguez ◽  
Hana Paculova ◽  
Sophie Kogut ◽  
Jessica Heath ◽  
Hilde Schjerven ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Molecular Mechanisms ◽  
Lymphoblastic Leukemia ◽  
Transcriptome Profiling ◽  
Rna Seq ◽  
Protein Coding ◽  
Non Coding Rna ◽  
Technological Developments ◽  
Cell Acute Lymphoblastic Leukemia

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell acute lymphoblastic leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Suppressed Immune-Related Profile Rescues Abortion-Prone Fetuses: A Novel Insight Into the CBA/J × DBA/2J Mouse Model

2019 ◽  
Vol 26 (11) ◽  
pp. 1485-1492
Author(s):  
Xiaochun Yi ◽  
Jie Zhang ◽  
Huixiang Liu ◽  
Tianxia Yi ◽  
Yuhua Ou ◽  
...  
Keyword(s):  
Immune System ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Poor Treatment ◽  
Polymerase Chain ◽  
Poor Treatment Outcome ◽  
Immune Related Genes ◽  
And Control ◽  
Upregulated Genes ◽  
Tgf Β1

The adverse clinical result and poor treatment outcome in recurrent spontaneous abortion (RSA) make it necessary to understand the pathogenic mechanism. The mating combination CBA/J × DBA/2 has been widely used as an abortion-prone model compared to DBA/2-mated CBA/J mice. Here, we used RNA-seq to get a comprehensive catalogue of genes differentially expressed between survival placenta in abortion-prone model and control. Five hundred twenty-four differentially expressed genes were obtained followed by clustering analysis, Gene Ontology analysis, and pathway analysis. We paid more attention to immune-related genes namely “immune response” and “immune system process” including 33 downregulated genes and 28 upregulated genes. Twenty-one genes contribute to suppressing immune system and 7 are against it. Six genes were validated by reverse transcription-polymerase chain reaction, namely Ccr1l1, Tlr4, Tgf-β1, Tyro3, Gzmb, and Il-1β. Furthermore, Tlr4, Tgf-β1, and Il-1β were analyzed by Western blot. Such immune profile gives us a better understanding of the complicated immune processing in RSA and immunosuppression can rescue pregnancy loss.

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