scholarly journals Spatially resolved transcriptome profiles of mammalian kidneys illustrate the molecular complexity of functional nephron segments, cell-to-cell interactions and genetic variants

2020 ◽  
Author(s):  
Arti M. Raghubar ◽  
Duy T. Pham ◽  
Xiao Tan ◽  
Laura F. Grice ◽  
Joanna Crawford ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Interaction Analysis ◽  
Variant Calling ◽  
Transcriptome Profiling ◽  
Cell Interaction ◽  
Spatial Context ◽  
Nephron Segments ◽  
Spatially Resolved ◽  
Differential Gene

AbstractUnderstanding the molecular mechanisms underlying mammalian kidney function requires transcriptome profiling of the interplay between cells comprising nephron segments. Traditional transcriptomics requires cell dissociation, resulting in loss of the spatial context of gene expression within native tissue. To address this problem, we performed spatial transcriptomics (ST) to retain the spatial context of the transcriptome in human and mouse kidneys. The generated ST data allowed spatially resolved differential gene expression analysis, spatial identification of functional nephron segments, cell-to-cell interaction analysis, and chronic kidney disease-associated genetic variant calling. Novel ST thus provides an opportunity to enhance kidney diagnostics and knowledge, by retaining the spatial context of gene expression within intact tissue.

scholarly journals The Western Diet Regulates Hippocampal Microvascular Gene Expression: An Integrated Genomic Analyses in Female Mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Saivageethi Nuthikattu ◽  
Dragan Milenkovic ◽  
John Rutledge ◽  
Amparo Villablanca
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Differential Expression ◽  
Differential Gene Expression ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Western Diet ◽  
Protein Coding ◽  
Female Mice ◽  
Differential Gene

AbstractHyperlipidemia is a risk factor for dementia, and chronic consumption of a Western Diet (WD) is associated with cognitive impairment. However, the molecular mechanisms underlying the development of microvascular disease in the memory centers of the brain are poorly understood. This pilot study investigated the nutrigenomic pathways by which the WD regulates gene expression in hippocampal brain microvessels of female mice. Five-week-old female low-density lipoprotein receptor deficient (LDL-R−/−) and C57BL/6J wild type (WT) mice were fed a chow or WD for 8 weeks. Metabolics for lipids, glucose and insulin were determined. Differential gene expression, gene networks and pathways, transcription factors, and non-protein coding RNAs were evaluated by genome-wide microarray and bioinformatics analysis of laser captured hippocampal microvessels. The WD resulted in differential expression of 2,412 genes. The majority of differential gene expression was attributable to differential regulation of cell signaling proteins and their transcription factors, approximately 7% was attributable to differential expression of miRNAs, and a lesser proportion was due to other non-protein coding RNAs, primarily long non-coding RNAs (lncRNAs) and small nucleolar RNAs (snoRNAs) not previously described to be modified by the WD in females. Our findings revealed that chronic consumption of the WD resulted in integrated multilevel molecular regulation of the hippocampal microvasculature of female mice and may provide one of the mechanisms underlying vascular dementia.

Differential gene expression profiling of adult murine hematopoietic stem cells

Blood ◽  
2002 ◽  
Vol 99 (2) ◽  
pp. 488-498 ◽  
Author(s):  
In-Kyung Park ◽  
Yaqin He ◽  
Fangming Lin ◽  
Ole D. Laerum ◽  
Qiang Tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Differential Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Cdna Clones ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Differential Gene

Abstract Hematopoietic stem cells (HSCs) have self-renewal capacity and multilineage developmental potentials. The molecular mechanisms that control the self-renewal of HSCs are still largely unknown. Here, a systematic approach using bioinformatics and array hybridization techniques to analyze gene expression profiles in HSCs is described. To enrich mRNAs predominantly expressed in uncommitted cell lineages, 54 000 cDNA clones generated from a highly enriched population of HSCs and a mixed population of stem and early multipotent progenitor (MPP) cells were arrayed on nylon membranes (macroarray or high-density array), and subtracted with cDNA probes derived from mature lineage cells including spleen, thymus, and bone marrow. Five thousand cDNA clones with very low hybridization signals were selected for sequencing and further analysis using microarrays on glass slides. Two populations of cells, HSCs and MPP cells, were compared for differential gene expression using microarray analysis. HSCs have the ability to self-renew, while MPP cells have lost the capacity for self-renewal. A large number of genes that were differentially expressed by enriched populations of HSCs and MPP cells were identified. These included transcription factors, signaling molecules, and previously unknown genes.

scholarly journals Deciphering spatial domains from spatially resolved transcriptomics with adaptive graph attention auto-encoder

2021 ◽  
Author(s):  
Kangning Dong ◽  
Shihua Zhang
Keyword(s):  
Gene Expression ◽  
Spatial Information ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Identification Accuracy ◽  
Spatial Context ◽  
Gene Expressions ◽  
Spatially Resolved ◽  
Spatial Domains

Recent advances in spatially resolved transcriptomics have enabled comprehensive measurements of gene expression patterns while retaining spatial context of tissue microenvironment. Deciphering the spatial context of spots in a tissue needs to use their spatial information carefully. To this end, we developed a graph attention auto- encoder framework STGATE to accurately identify spatial domains by learning low-dimensional latent embeddings via integrating spatial information and gene expression profiles. To better characterize the spatial similarity at the boundary of spatial domains, STGATE adopts an attention mechanism to adaptively learn the similarity of neighboring spots, and an optional cell type-aware module through integrating the pre-clustering of gene expressions. We validated STGATE on diverse spatial transcriptomics datasets generated by different platforms with different spatial resolutions. STGATE could substantially improve the identification accuracy of spatial domains, and denoise the data while preserving spatial expression patterns. Importantly, STGATE could be extended to multiple consecutive sections for reducing batch effects between sections and extracting 3D expression domains from the reconstructed 3D tissue effectively.

scholarly journals The daily timing of gene expression and physiology in mammals

2007 ◽  
Vol 9 (3) ◽  
pp. 257-272 ◽  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Transcriptome Profiling ◽  
Temporal Organization ◽  
Daily Rhythms ◽  
Xenobiotic Detoxification ◽  
Peripheral Oscillators ◽  
Cyclic Gene ◽  
Circadian Timing System

Mammalian behavior and physiology undergo daily rhythms that are coordinated by an endogenous circadian timing system. This system has a hierarchical structure, in that a master pacemaker, residing in the suprachiasmatic nucleus of the ventral hypothalamus, synchronizes peripheral oscillators in virtually all body cells. While the basic molecular mechanisms generating the daily rhythms are similar in all cells, most clock outputs are cell-specific. This conclusion is based on genome-wide transcriptome profiling studies in several tissues that have revealed hundreds of rhythmically expressed genes. Cyclic gene expression in the various organs governs overt rhythms in behavior and physiology, encompassing sleep-wake cycles, metabolism, xenobiotic detoxification, and cellular proliferation. As a consequence, chronic perturbation of this temporal organization may lead to increased morbidity and reduced lifespan.

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