scholarly journals Comparison of human and mouse tissues with focus on genes with no 1-to-1 homology

2021 ◽  
Author(s):  
Jieun Jeong ◽  
Manolis Kellis

We assembled a panel of 28 tissue pairs of human and mouse with RNA-Seq data on gene expression. We focused on genes with no 1-to-1 homology, because they pose special challenges. In this way, we identified expression patterns that identify and explain differences between the two species and suggest target genes for therapeutic applications. Here we mention three examples. One pattern is observed by defining the aggregate expression of immunoglobulin genes (which have no homology) as a measure of different levels of an immune response. In Lung, we used this statistic to find genes that have significantly higher expression in low/moderate response, and thus they may be therapy targets: increasing their expression or mimicking their function with medications may help in recovery from inflammation in the lungs. Some of the observed associations are common to human and mouse; other associations involve genes involved in cell-to-cell signaling or in regeneration but were not known to be important in Lung. Second pattern is that in the Small Intestine, mouse expresses much less antimicrobial defensins, while it has much higher expression of enzymes that are found to improve adaptive immune response. Such enzymes may be tested if they improve probiotic supplements that help in gut inflammation and other diseases. Another pattern involves a many-to-many homology group of defensins that did not have a described function. In human tissues, expression of its genes was found only in a study of a disease of hair covered skin, but several of its genes are highly expressed in two tissues of our panel: mouse Skin and to a lesser degree mouse Vagina. This suggests that those genes or their homologs in other species may provide non-antibiotic medications for hair covered skin and other tissues with microbiome that includes fungi.

2017 ◽  
Author(s):  
Pradipta Ray ◽  
Andrew Torck ◽  
Lilyana Quigley ◽  
Andi Wangzhou ◽  
Matthew Neiman ◽  
...  

AbstractMolecular neurobiological insight into human nervous tissues is needed to generate next generation therapeutics for neurological disorders like chronic pain. We obtained human Dorsal Root Ganglia (DRG) samples from organ donors and performed RNA-sequencing (RNA-seq) to study the human DRG (hDRG) transcriptional landscape, systematically comparing it with publicly available data from a variety of human and orthologous mouse tissues, including mouse DRG (mDRG). We characterized the hDRG transcriptional profile in terms of tissue-restricted gene co-expression patterns and putative transcriptional regulators, and formulated an information-theoretic framework to quantify DRG enrichment. Our analyses reveal an hDRG-enriched protein-coding gene set (~140), some of which have not been described in the context of DRG or pain signaling. A majority of these show conserved enrichment in mDRG, and were mined for known drug - gene product interactions. Comparison of hDRG and tibial nerve transcriptomes suggest pervasive mRNA transport of sensory neuronal genes to axons in adult hDRG, with potential implications for mechanistic insight into chronic pain in patients. Relevant gene families and pathways were also analyzed, including transcription factors (TFs), g-protein coupled receptors (GCPRs) and ion channels. We present our work as an online, searchable repository (http://www.utdallas.edu/bbs/painneurosciencelab/DRGtranscriptome), creating a valuable resource for the community. Our analyses provide insight into DRG biology for guiding development of novel therapeutics, and a blueprint for cross-species transcriptomic analyses.SummaryWe generated RNA sequencing data from human DRG samples and comprehensively compared this transcriptome to other human tissues and a matching panel of mouse tissues. Our analysis uncovered functionally enriched genes in the human and mouse DRG with important implications for understanding sensory biology and pain drug discovery.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Luciana D’Apice ◽  
Valerio Costa ◽  
Rossella Sartorius ◽  
Maria Trovato ◽  
Marianna Aprile ◽  
...  

The filamentous bacteriophage fd, codisplaying antigenic determinants and a single chain antibody fragment directed against the dendritic cell receptor DEC-205, is a promising vaccine candidate for its safety and its ability to elicit innate and adaptive immune response in absence of adjuvants. By using a system vaccinology approach based on RNA-Sequencing (RNA-Seq) analysis, we describe a relevant gene modulation in dendritic cells pulsed with anti-DEC-205 bacteriophages fd. RNA-Seq data analysis indicates that the bacteriophage fd virions are sensed as a pathogen by dendritic cells; they activate the danger receptors that trigger an innate immune response and thus confer a strong adjuvanticity that is needed to obtain a long-lasting adaptive immune response.


Endocrinology ◽  
2004 ◽  
Vol 145 (2) ◽  
pp. 941-950 ◽  
Author(s):  
Andrzej Slominski ◽  
Alexander Pisarchik ◽  
Desmond J. Tobin ◽  
Joseph E. Mazurkiewicz ◽  
Jacobo Wortsman

Abstract We completed the mapping of a cutaneous CRH signaling system in two species with widely different determinants of skin functions, humans and mice. In human skin, the CRH receptor (CRH-R) 1 was expressed in all major cellular populations of epidermis, dermis, and subcutis with CRH-R1α being the most prevalent isoform. The CRH-R2 gene was expressed solely in hair follicle keratinocytes and papilla fibroblasts, whereas CRH-R2 antigen was localized predominantly in hair follicles, sebaceous and eccrine glands, muscle and blood vessels. In mouse skin, the CRH-R2 gene and protein were widely expressed in all cutaneous compartments and in cultured normal and malignant melanocytes. CRH-binding protein mRNA was present in dermal fibroblasts, melanoma cells, and sc fat of human skin and undetectable in mouse skin. The urocortin II gene was expressed equally in mouse and human skin. Taken together with our previous investigations, the present studies document the preferential expression of CRH-R1 in human skin, which mirrors CRH-R2 expression patterns in human and mouse skin. They are likely reflecting different functional activities of human and mouse skin. The adnexal location of CRH-R2 suggests a role for the receptor in hair growth. The differential interspecies CRH signaling expression pattern probably reflects adaptation to species-specific skin function determinants.


2019 ◽  
Author(s):  
Dharanidhar Dang ◽  
Sahar Taheri ◽  
Soumita Das ◽  
Pradipta Ghosh ◽  
Lawrence S. Prince ◽  
...  

ABSTRACTMacrophages are a type of white blood cell, of the immune system, that engulfs and digests cellular debris, cancer cells, and anything else that does not have the type of proteins specific to healthy body cells on its surface. Understanding gene expression dynamics in macrophages are crucial for studying human diseases. Recent advances in high-throughput technologies have enabled the collection of immense amounts of biological data. A reliable marker of macrophage is essential to study their function. Traditional approaches use a number of markers that may have tissue specific expression patterns. To identify universal biomarker of macrophage, we used a previously published computational approach called BECC (Boolean Equivalent Correlated Clusters) that was originally used to identify universal cell cycle genes. We performed BECC analysis on a seed gene CD14, a known macrophage marker. FCER1G and TYROBP were among the top candidates which were validated as strong candidates for universal biomarkers for macrophages in human and mouse tissues. To our knowledge, such a finding is first of its kind.CONTRIBUTIONS TO THE FIELDWe have developed a computational approach to identify universal biomarkers of different entities in a biological system. We applied this approach to study macrophages and identified universal biomarkers of this particular cell type. FCER1G and TYROBP were among the top candidates which were validated as strong candidates for universal biomarkers for macrophages in human and mouse tissues. The expression patterns of TYROBP and FCER1G are found to be more homogeneous compared to currently used biomarkers such as ITGAM, EMR1 (F4/80), and CD68. Further, we demonstrated that this homogeneity extends to all the tissues currently profiled in the public domain in multiple species including human and mouse. FCER1G and TYROBP expression patterns were also found to be extremely specific to macrophages found in various tissues. They are strongly co-expressed together. We believe that these two genes are the most reliable candidates of universal biomarker for macrophages.


2020 ◽  
Author(s):  
Canbin Chen ◽  
Fangfang Xie ◽  
Qingzhu Hua ◽  
Noemi Tel Zur ◽  
Lulu Zhang ◽  
...  

Abstract Background: MicroRNAs (miRNAs) and their regulatory functions in anthocyanin, carotenoid, and chlorophyll accumulation have been extensively characterized in many plant species. However, the miRNA regulatory mechanism in betalain biosynthesis remains mostly unknown. Results: In this study, 126 conserved miRNAs and 41 novel miRNAs were first isolated from Hylocereus monacanthus, among which 95 conserved miRNAs belonged to 53 miRNA families. 34 candidate miRNAs related to betalain biosynthesis were found to be differentially expressed. The expression patterns of those differential expressed miRNAs were analyzed in various tissues of the pitaya by RT-qPCR. A significantly negative correlation was detected between the expression levels of half those miRNAs and corresponding target genes. Target genes of miRNAs i.e. aly-miR157d-5p_L+1_1ss4AC-comp25631_c0, aau-miR160_L-4R+ 1-comp36993_c0_seq3, nta-miR6020b-comp234190_c0, PC-5p-192_7269-comp29967_c0, PC-5p-23845_39-comp28219_c0, mdm-miR828a_1ss22AT-comp24967_c0, mdm-miR858- comp15143_c0, mdm-miR858-comp24362_c0 and mdm-miR858-comp403340_c0 were verified by 5′RACE and transient expression system in tobacco.Conclusions: aly-miR157d-5p_L+1_1ss4AC, aau-miR160_L-4R+1, nta-miR6020b PC-5p-192_7269, PC-5p-23845_39, mdm-miR828a_1ss22AT and mdm-miR858 may play important roles in pitaya fruit coloration and betalain accumulation. Our findings provide insights into the roles of miRNAs and their target genes of regulatory functions involved in betalain biosynthesis of pitaya.


2017 ◽  
Author(s):  
Nisar Wani ◽  
Khalid Raza

AbstractGene expression patterns determine the manner whereby organisms regulate various cellular processes and therefore their organ functions.These patterns do not emerge on their own, but as a result of diverse regulatory factors such as, DNA binding proteins known as transcription factors (TF), chromatin structure and various other environmental factors. TFs play a pivotal role in gene regulation by binding to different locations on the genome and influencing the expression of their target genes. Therefore, predicting target genes and their regulation becomes an important task for understanding mechanisms that control cellular processes governing both healthy and diseased cells.In this paper, we propose an integrated inference pipeline for predicting target genes and their regulatory effects for a specific TF using next-generation data analysis tools.


2019 ◽  
Author(s):  
Wenfa Ng

Snippets of virus that infect humans have been shown to be incorporated into the human genome. Could such virus snippets provide a form of adaptive immunity similar to that offered by CRISPR to bacterial cells? To answer the question, RNA-seq could be used to provide a broad view of the RNA transcribed from DNA in the genome. Using known genome sequence of viruses that infect humans as template, reads obtained from RNA-seq would be profiled for virus snippets integrated into human genome and subsequently transcribed as part of an adaptive immune system. Subsequently, viruses corresponding to the virus snippets in human genome would be used to infect human cell lines to obtain direct evidence of how virus snippets mediate an adaptive immune response at the cellular level. Specifically, successful defence of the cell by virus snippets triggering an adaptive immune response would manifest as viable cells compared to lysed cells unable to mount an immune response. Following demonstration of cell viability under viral challenge, in vitro biochemical assays using cell lysate would interrogate the specific proteins and enzymes that mediate possible cutting of the foreign DNA or RNA. To this end, beads immobilized with virus snippets would serve as bait for binding to complementary viral DNA or RNA as well as potential endogenous endonuclease protein. Following precipitation and recovery of beads, possible endonuclease that bind to both viral DNA or RNA and virus snippets immobilized on beads would be isolated through gel electrophoresis and subsequently purified. Purified endonuclease would be assayed for activity against a variety of nucleic acids (both DNA and RNA) from various sources with and without added virus snippets. This provides important information on substrate range and specificity of the potential endonuclease. Amino acid sequencing of the purified endonuclease would help downstream bioinformatic search for candidate protein in the human genome. Finally, cryo-electron microscopy could help determine the structure of the endonuclease in complex with viral nucleic acids and virus snippets. Such structural information would provide more insights into mechanistic details describing the binding and cleavage of viral DNA or RNA in a CRISPR-like adaptive immune response in human cells. Overall, tantalizing clues have emerged that a CRISPR-like adaptive immune response may exist in human cells for defending against viral attack. Combination of cell biological, biochemical and structural tools could lend insights into the potential endonuclease that mediate double strand break of foreign DNA or RNA using virus snippets transcribed from the human genome as guide RNA. If demonstrated to be true for a variety of human viruses across different cell lines, the newly discovered viral defence mechanism in human cells hold important implications for understanding the adoption and evolution of CRISPR in eukaryotic cells.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9585
Author(s):  
Wei Xia ◽  
Yajing Dou ◽  
Rui Liu ◽  
Shufang Gong ◽  
Dongyi Huang ◽  
...  

Long noncoding RNAs (lncRNAs) are an important class of genes and play important roles in a range of biological processes. However, few reports have described the identification of lncRNAs in oil palm. In this study, we applied strand specific RNA-seq with rRNA removal to identify 1,363 lncRNAs from the equally mixed tissues of oil palm spear leaf and six different developmental stages of mesocarp (8–24 weeks). Based on strand specific RNA-seq data and 18 released oil palm transcriptomes, we systematically characterized the expression patterns of lncRNA loci and their target genes. A total of 875 uniq target genes for natural antisense lncRNAs (NAT-lncRNA, 712), long intergenic noncoding RNAs (lincRNAs, 92), intronic-lncRNAs (33), and sense-lncRNAs (52) were predicted. A majority of lncRNA loci (77.8%–89.6%) had low expression in 18 transcriptomes, while only 89 lncRNA loci had medium to high expression in at least one transcriptome. Coexpression analysis between lncRNAs and their target genes indicated that 6% of lncRNAs had expression patterns positively correlated with those of target genes. Based on single nucleotide polymorphism (SNP) markers derived from our previous research, 6,882 SNPs were detected for lncRNAs and 28 SNPs belonging to 21 lncRNAs were associated with the variation of fatty acid contents. Moreover, seven lncRNAs showed expression patterns positively correlated expression pattern with those of genes in de novo fatty acid synthesis pathways. Our study identified a collection of lncRNAs for oil palm and provided clues for further research into lncRNAs that may regulate mesocarp development and lipid metabolism.


2019 ◽  
Vol 20 (23) ◽  
pp. 5864 ◽  
Author(s):  
Yuliang Wang ◽  
Abdiasis M. Hussein ◽  
Logeshwaran Somasundaram ◽  
Rithika Sankar ◽  
Damien Detraux ◽  
...  

microRNAs are ~22bp nucleotide non-coding RNAs that play important roles in the post-transcriptional regulation of gene expression. Many studies have established that microRNAs are important for cell fate choices, including the naïve to primed pluripotency state transitions, and their intermediate state, the developmentally suspended diapause state in early development. However, the full extent of microRNAs associated with these stage transitions in human and mouse remain under-explored. By meta-analysis of microRNA-seq, RNA-seq, and metabolomics datasets from human and mouse, we found a set of microRNAs, and importantly, their experimentally validated target genes that show consistent changes in naïve to primed transitions (microRNA up, target genes down, or vice versa). The targets of these microRNAs regulate developmental pathways (e.g., the Hedgehog-pathway), primary cilium, and remodeling of metabolic processes (oxidative phosphorylation, fatty acid metabolism, and amino acid transport) during the transition. Importantly, we identified 115 microRNAs that significantly change in the same direction in naïve to primed transitions in both human and mouse, many of which are novel candidate regulators of pluripotency. Furthermore, we identified 38 microRNAs and 274 target genes that may be involved in diapause, where embryonic development is temporarily suspended prior to implantation to uterus. The upregulated target genes suggest that microRNAs activate stress response in the diapause stage. In conclusion, we provide a comprehensive resource of microRNAs and their target genes involved in naïve to primed transition and in the paused intermediate, the embryonic diapause stage.


2004 ◽  
Vol 33 (3) ◽  
pp. 609-622 ◽  
Author(s):  
Knut R Steffensen ◽  
Soek Ying Neo ◽  
Thomas M Stulnig ◽  
Vinsensius B Vega ◽  
Safia S Rahman ◽  
...  

The liver X receptors α and β (LXRα and LXRβ ) are members of the nuclear receptor superfamily of proteins which are highly expressed in metabolically active tissues. They regulate gene expression of critical genes involved in cholesterol catabolism and transport, lipid and triglyceride biosynthesis and carbohydrate metabolism in response to distinct oxysterols and intermediates in the cholesterol metabolic pathway. The biological roles of the LXRs in tissues other than liver, intestine and adipose tissue are poorly elucidated. In this study we used global gene-expression profiling analysis to detect differences in expression patterns in several tissues from mice fed an LXR agonist or vehicle. Our results show that LXR plays an important role in the kidney, lung, adrenals, brain, testis and heart where several putative LXR target genes were found. The effects of the LXRs were further analysed in adrenals where treatment with an LXR agonist induced expression of adrenocorticotrophic hormone receptor, suppressed expression of uncoupling protein (UCP)-1 and UCP-3 as well as several glycolytic enzymes and led to increased serum corticosterone levels. These results indicate novel biological roles of the LXR including regulation of energy metabolism, glycolysis and steroidogenesis in the adrenals via alteration of expression profiles of putative target genes.


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