Using RNA-seq to determine patterns of sex-bias in gene expression in the brain of the sex-role reversed Gulf Pipefish (Syngnathus scovelli)

AbstractNon-small cell lung cancer (NSCLC) metastatic to the brain leptomeninges is rapidly fatal, cannot be biopsied, and cancer cells in the cerebrospinal fluid (CSF) are few; therefore, available tissue samples to develop effective treatments are severely limited. This study aimed to converge single-cell RNA-seq and cell-free RNA (cfRNA) analyses to both diagnose NSCLC leptomeningeal metastases (LM), and to use gene expression profiles to understand progression mechanisms of NSCLC in the brain leptomeninges. NSCLC patients with suspected LM underwent withdrawal of CSF via lumbar puncture. Four cytology-positive CSF samples underwent single-cell capture (n = 197 cells) by microfluidic chip. Using robust principal component analyses, NSCLC LM cell gene expression was compared to immune cells. Massively parallel qPCR (9216 simultaneous reactions) on human CSF cfRNA samples compared the relative gene expression of patients with NSCLC LM (n = 14) to non-tumor controls (n = 7). The NSCLC-associated gene, CEACAM6, underwent in vitro validation in NSCLC cell lines for involvement in pathologic behaviors characteristic of LM. NSCLC LM gene expression revealed by single-cell RNA-seq was also reflected in CSF cfRNA of cytology-positive patients. Tumor-associated cfRNA (e.g., CEACAM6, MUC1) was present in NSCLC LM patients’ CSF, but not in controls (CEACAM6 detection sensitivity 88.24% and specificity 100%). Cell migration in NSCLC cell lines was directly proportional to CEACAM6 expression, suggesting a role in disease progression. NSCLC-associated cfRNA is detectable in the CSF of patients with LM, and corresponds to the gene expression profile of NSCLC LM cells. CEACAM6 contributes significantly to NSCLC migration, a hallmark of LM pathophysiology.

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Age-related changes of gene expression in the neocortex: Preliminary data on RNA-Seq of the transcriptome in three functionally distinct cortical areas

Development and Psychopathology ◽

10.1017/s0954579412000818 ◽

2012 ◽

Vol 24 (4) ◽

pp. 1427-1442 ◽

Cited By ~ 19

Author(s):

Oksana Yu. Naumova ◽

Dean Palejev ◽

Natalia V. Vlasova ◽

Maria Lee ◽

Sergei Yu. Rychkov ◽

...

Keyword(s):

Gene Expression ◽

Molecular Mechanisms ◽

Rna Seq ◽

Signaling Systems ◽

Cortical Areas ◽

Age Related ◽

Transcriptional Changes ◽

Atypical Development ◽

The Brain ◽

Age Related Changes

AbstractThe study of gene expression (i.e., the study of the transcriptome) in different cells and tissues allows us to understand the molecular mechanisms of their differentiation, development and functioning. In this article, we describe some studies of gene-expression profiling for the purposes of understanding developmental (age-related) changes in the brain using different technologies (e.g., DNA-Microarray) and the new and increasingly popular RNA-Seq. We focus on advancements in studies of gene expression in the human brain, which have provided data on the structure and age-related variability of the transcriptome in the brain. We present data on RNA-Seq of the transcriptome in three distinct areas of the neocortex from different ages: mature and elderly individuals. We report that most age-related transcriptional changes affect cellular signaling systems, and, as a result, the transmission of nerve impulses. In general, the results demonstrate the high potential of RNA-Seq for the study of distinctive features of gene expression among cortical areas and the changes in expression through normal and atypical development of the central nervous system.

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Gut-derived Metabolites Influence Neurodevelopmental Gene Expression and Wnt Signalling Events in a Germ-free Zebrafish Model

10.21203/rs.3.rs-1250656/v1 ◽

2022 ◽

Author(s):

Terry Van Raay ◽

Victoria Rea ◽

Ian Bell

Keyword(s):

Gene Expression ◽

Neural Development ◽

Morphological Changes ◽

Wnt Signalling ◽

Gene Ontology Analysis ◽

Rna Seq ◽

Zebrafish Model ◽

Germ Free ◽

The Impact ◽

The Brain

Abstract Background : Small molecule metabolites produced by the microbiome are known to be neuroactive and are capable of directly impacting the brain and central nervous system, yet there is little data on the contribution of these metabolites to the earliest stages of neural development and neural gene expression. Here, we explore the impact of deriving zebrafish embryos in the absence of microbes on early neural development as well as investigate whether any potential changes can be rescued with treatment of metabolites derived from the zebrafish gut microbiota. Results : Overall, we did not observe any gross morphological changes between treatments but did observe a significant decrease in neural gene expression in embryos raised germ-free, which was rescued with the addition of zebrafish metabolites. Specifically, we identified 354 genes significantly down regulated in germ-free embryos compared to conventionally raised embryos via RNA-Seq analysis. Of these, 42 were rescued with a single treatment of zebrafish gut-derived metabolites to germ-free embryos. Gene ontology analysis revealed that these genes are involved in prominent neurodevelopmental pathways including transcriptional regulation and Wnt signalling. Consistent with the ontology analysis, we found alterations in the development of Wnt dependent events which was rescued in the germ-free embryos treated with metabolites. Conclusions : These findings demonstrate that gut-derived metabolites are in part responsible for regulating critical signalling pathways in the brain, especially during neural development.

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gEAR: gene Expression Analysis Resource portal for community-driven, multi-omic data exploration

10.1101/2020.08.28.272039 ◽

2020 ◽

Cited By ~ 1

Author(s):

Joshua Orvis ◽

Brian Gottfried ◽

Jayaram Kancherla ◽

Ricky S. Adkins ◽

Yang Song ◽

...

Keyword(s):

Gene Expression ◽

Expression Analysis ◽

Gene Expression Analysis ◽

De Novo ◽

Marker Gene ◽

Rna Seq ◽

Data Types ◽

Multiple Species ◽

User Friendly ◽

The Brain

ABSTRACTThe gEAR portal (gene Expression Analysis Resource, umgear.org) is an open access community-driven tool for multi-omic and multi-species data visualization, analysis and sharing. The gEAR supports visualization of multiple RNA-seq data types (bulk, sorted, single cell/nucleus) and epigenomics data, from multiple species, time points and tissues in a single-page, user-friendly browsable format. An integrated scRNA-seq workbench provides access to raw data of scRNA-seq datasets for de novo analysis, as well as marker-gene and cluster comparisons of pre-assigned clusters. Users can upload, view, analyze and privately share their own data in the context of previously published datasets. Short, permanent URLs can be generated for dissemination of individual or collections of datasets in published manuscripts. While the gEAR is currently curated for auditory research with over 90 high-value datasets organized in thematic profiles, the gEAR also supports the BRAIN initiative (via nemoanalytics.org) and is easily adaptable for other research domains.

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Gut-derived metabolites influence neurodevelopmental gene expression and Wnt signalling events in a germ-free zebrafish model

10.1101/2021.07.06.451297 ◽

2021 ◽

Author(s):

Victoria Rea ◽

Ian Bell ◽

Terence J Van Raay

Keyword(s):

Gene Expression ◽

Neural Development ◽

Morphological Changes ◽

Wnt Signalling ◽

Gene Ontology Analysis ◽

Rna Seq ◽

Zebrafish Model ◽

Germ Free ◽

The Impact ◽

The Brain

Small molecule metabolites produced by the microbiome are known to be neuroactive and are capable of directly impacting the brain and central nervous system, yet there is little data on the contribution of these metabolites to the earliest stages of neural development and neural gene expression. Here, we explore the impact of rearing zebrafish embryos in the absence of microbes on early neural development as well as investigate whether any potential changes can be rescued with treatment of metabolites derived from the zebrafish gut microbiota. Overall, we did not observe any gross morphological changes between treatments but did observe a significant decrease in neural gene expression in embryos raised germ-free, which was rescued with the addition of zebrafish metabolites. Specifically, we identified 361 genes significantly down regulated in GF embryos compared to conventionally raised embryos via RNA-Seq analysis. Of these, 42 were rescued with the treatment of zebrafish gut-derived metabolites to GF embryos. Gene ontology analysis revealed that these genes are involved in prominent neurodevelopmental pathways including transcriptional regulation and Wnt signalling. Consistent with the ontology analysis, we found alterations in the development of Wnt dependent events which is rescued in the GF embryos treated with metabolites.

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Comparison of mouse models reveals a molecular distinction between psychotic illness in PWS and schizophrenia

Translational Psychiatry ◽

10.1038/s41398-021-01561-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Simona K. Zahova ◽

Trevor Humby ◽

Jennifer R. Davies ◽

Joanne E. Morgan ◽

Anthony R. Isles

Keyword(s):

Gene Expression ◽

Psychiatric Illness ◽

Neurodevelopmental Disorder ◽

Therapeutic Interventions ◽

Rna Seq ◽

Wild Type ◽

Psychotic Illness ◽

Over Expression ◽

Transcriptional Changes ◽

The Brain

AbstractPrader-Willi Syndrome (PWS) is a neurodevelopmental disorder caused by mutations affecting paternal chromosome 15q11-q13, and characterized by hypotonia, hyperphagia, impaired cognition, and behavioural problems. Psychotic illness is a challenging problem for individuals with PWS and has different rates of prevalence in distinct PWS genotypes. Previously, we demonstrated behavioural and cognitive endophenotypes of relevance to psychiatric illness in a mouse model for one of the associated PWS genotypes, namely PWS-IC, in which deletion of the imprinting centre leads to loss of paternally imprinted gene expression and over-expression of Ube3a. Here we examine the broader gene expression changes that are specific to the psychiatric endophenotypes seen in this model. To do this we compared the brain transcriptomic profile of the PWS-IC mouse to the PWS-cr model that carries a deletion of the PWS minimal critical interval spanning the snoRNA Snord116 and Ipw. Firstly, we examined the same behavioural and cognitive endophenotypes of relevance to psychiatric illness in the PWS-cr mice. Unlike the PWS-IC mice, PWS-cr exhibit no differences in locomotor activity, sensory-motor gating, and attention. RNA-seq analysis of neonatal whole brain tissue revealed a greater number of transcriptional changes between PWS-IC and wild-type littermates than between PWS-cr and wild-type littermates. Moreover, the differentially expressed genes in the PWS-IC brain were enriched for GWAS variants of episodes of psychotic illness but, interestingly, not schizophrenia. These data illustrate the molecular pathways that may underpin psychotic illness in PWS and have implications for potential therapeutic interventions.

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Evidence of sex-bias in gene expression in the brain transcriptome of two populations of rainbow trout (Oncorhynchus mykiss) with divergent life histories

PLoS ONE ◽

10.1371/journal.pone.0193009 ◽

2018 ◽

Vol 13 (2) ◽

pp. e0193009 ◽

Cited By ~ 5

Author(s):

Matthew C. Hale ◽

Garrett J. McKinney ◽

Frank P. Thrower ◽

Krista M. Nichols

Keyword(s):

Gene Expression ◽

Rainbow Trout ◽

Oncorhynchus Mykiss ◽

Life Histories ◽

Sex Bias ◽

Rainbow Trout Oncorhynchus Mykiss ◽

Brain Transcriptome ◽

The Brain ◽

Two Populations

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Correspondence between resting state activity and brain gene expression

10.1101/021071 ◽

2015 ◽

Author(s):

Guang-Zhong Wang ◽

T. Grant Belgard ◽

Deng Mao ◽

Leslie Chen ◽

Stefano Berto ◽

...

Keyword(s):

Gene Expression ◽

Resting State ◽

Brain Activity ◽

Low Frequency ◽

Population Level ◽

Rna Seq ◽

Brain Gene Expression ◽

Functional Brain Activity ◽

The Relationship ◽

The Brain

The relationship between functional brain activity and gene expression has not been fully explored in the human brain. Here, we identify significant correlations between gene expression in the brain and functional activity by comparing fractional Amplitude of Low Frequency Fluctuations (fALFF) from two independent human fMRI resting state datasets to regional cortical gene expression from a newly generated RNA-seq dataset and two additional gene expression datasets to obtain robust and reproducible correlations. We find significantly more genes correlated with fALFF than expected by chance, and identify specific genes correlated with the imaging signals in multiple expression datasets in the default mode network. Together, these data support a population-level relationship between regional steady state brain gene expression and resting state brain activity.

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