Massive mining of publicly available RNA-seq data from human and mouse

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.

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Role of IgE-FcεR1 in Pathological Cardiac Remodeling and Dysfunction

Circulation ◽

10.1161/circulationaha.120.047852 ◽

2020 ◽

Author(s):

Hongmei Zhao ◽

Hongqin Yang ◽

Chi Geng ◽

Yang Chen ◽

Junling Pang ◽

...

Keyword(s):

Cardiac Remodeling ◽

Causative Role ◽

Ang Ii ◽

Rna Seq ◽

Ige Receptor ◽

Ige Antibodies ◽

Serum Ige ◽

Human And Mouse

Background: Immunoglobulin E (IgE) belongs to a class of immunoglobulins involved in immune response to specific allergens. However, the roles of IgE and IgE receptor (FcεR1) in pathological cardiac remodeling and heart failure (HF) are unknown. Methods: Serum IgE levels and cardiac IgE receptor (FcεR1) expression were assessed in diseased hearts from human and mouse. The role of FcεR1 signaling in pathological cardiac remodeling was explored in vivo by FcεR1 genetic depletion, anti-IgE antibodies, and bone-marrow (BM) transplantation. The roles of IgE-FcεR1 pathway were further evaluated in vitro in primary cultured rat cardiomyocytes (CMs) and cardiac fibroblasts (CFs). RNA-seq and bioinformatic analyses were used to identify biochemical changes and signaling pathways that are regulated by IgE/FcεR1. Results: Serum IgE levels were significantly elevated in patients with HF as well as in two mouse cardiac disease models induced by chronic pressure overload via transverse aortic contraction (TAC) and chronic angiotensin II (Ang II) infusion. Interestingly, FcεR1 expression levels were also significantly up-regulated in failing hearts from human and mouse. Blockade of the IgE-FcεR1 pathway by FcεR1 knockout alleviated TAC- or Ang II-induced pathological cardiac remodeling and/or dysfunction. Anti-IgE antibodies (including the clinical drug, omalizumab) also significantly alleviated Ang II-induced cardiac remodeling. BM transplantation experiments indicated that IgE-induced cardiac remodeling was mediated through non-BM-derived cells. FcεR1 was found to be expressed in both CMs and CFs. In cultured rat CMs, IgE-induced CM hypertrophy and hypertrophic marker expression were abolished by depleting FcεR1. In cultured rat CFs, IgE-induced CF activation and matrix protein production were also blocked by FcεR1 deficiency. RNA-seq and signaling pathway analyses revealed that transforming growth factor-β (TGF-β) may be a critical mediator and blocking TGF-β indeed alleviated IgE-induced cardiomyocyte hypertrophy and cardiac fibroblast activation in vitro . Conclusions: Our findings suggest that IgE induction plays a causative role in pathological cardiac remodeling, at least partially via the activation of IgE-FcεR1 signaling in CMs and CFs. Therapeutic strategies targeting the IgE-FcεR1 axis may be effective for managing IgE-mediated cardiac remodeling.

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Rowley JW, Oler AJ, Tolley ND, et al. Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes. Blood. 2011;118(14):e101-e111.

Blood ◽

10.1182/blood-2014-04-573402 ◽

2014 ◽

Vol 123 (24) ◽

pp. 3843-3843

Keyword(s):

Rna Seq ◽

Genome Wide ◽

Human And Mouse

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A map of gene expression in neutrophil-like cell lines

10.1101/204875 ◽

2017 ◽

Cited By ~ 1

Author(s):

Esther Rincón ◽

Briana Rocha-Gregg ◽

Sean R. Collins

Keyword(s):

Gene Expression ◽

Cell Viability ◽

Cell Lines ◽

Gene Expression Pattern ◽

Cell Surface Expression ◽

Human Neutrophils ◽

Published Data ◽

Rna Seq ◽

Gene Expression Database ◽

Human And Mouse

AbstractBackgroundHuman neutrophils are central players in innate immunity, a major component of inflammatory responses, and a leading model for cell motility and chemotaxis. However, primary neutrophils are remarkably short-lived, limiting their experimental usefulness in the laboratory. Thus, human myeloid cell lines have been established and characterized for their ability to undergo neutrophil-like differentiationin vitro. The HL-60 cell line and its PLB-985 sub-line are commonly used as a model for human neutrophil behavior, but how closely gene expression in differentiated cells resembles that of primary neutrophils has remained unclear.ResultsIn the present study, we compared the effectiveness of differentiation protocols and used RNA sequencing (RNA-seq) to compare the transcriptomes of HL-60 and PLB-985 cells with published data for human and mouse primary neutrophils. Among commonly used differentiation protocols for neutrophil like cell lines, addition of dimethyl sulfoxide (DMSO) gave the best combination of cell viability and expression of markers for differentiation. However, combining DMSO with the serum-free-supplement Nutridoma resulted in an increased chemotactic response and cell surface expression of the neutrophil markers FPR1 and CD11b without a cost in viability. RNA-seq analysis of HL-60 and PLB-985 cells before and after differentiation showed that differentiation broadly increases the similarity in gene expression between the cell lines and primary neutrophils. Furthermore, the gene expression pattern of the differentiated cell lines correlated slightly better with that of human neutrophils than the mouse neutrophil pattern did. Finally, we created a publicly available gene expression database that is searchable by gene name and by protein domain content, where users can compare gene expression in HL-60, PLB-985 and primary human and mouse neutrophils.ConclusionsOur study verifies that a DMSO-based differentiation protocol for HL-60 and PLB-985 cell lines gives superior differentiation and cell viability relative to other common protocols, and indicates that addition of Nutridoma may be preferable for studies of chemotaxis. Our neutrophil gene expression database will be a valuable tool to identify similarities and differences in gene expression between the cell lines and primary neutrophils, to compare expression levels for genes of interest, and to improve the design of tools for genetic perturbations.

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RiboSeqDB – a repository of selected human and mouse ribosome footprint and RNA-seq data

Virtual Biology ◽

10.12704/vb/e18 ◽

2014 ◽

Vol 1 (2) ◽

pp. 37 ◽

Cited By ~ 4

Author(s):

Ruslan N Sharipov ◽

Ivan S Yevshin ◽

Yury V Kondrakhin ◽

Oxana A Volkova

Keyword(s):

Rna Seq ◽

Human And Mouse

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HRT Atlas v1.1 database: redefining human and mouse housekeeping genes and candidate reference transcripts by mining massive RNA-seq datasets

10.1101/787150 ◽

2019 ◽

Author(s):

Bidossessi Wilfried Hounkpe ◽

Francine Chenou ◽

Franciele Lima ◽

Erich Vinicius de Paula

Keyword(s):

Gene Expression ◽

Wild Type Mouse ◽

Housekeeping Genes ◽

Regulatory Elements ◽

Data Sets ◽

Rna Seq ◽

Cellular Functions ◽

Evolutionary Features ◽

Small Device ◽

Human And Mouse

AbstractHousekeeping (HK) genes are constitutively expressed genes that are required for the maintenance of basic cellular functions. Despite their importance in the calibration of gene expression, as well as the understanding of many genomic and evolutionary features, important discrepancies have been observed in studies that previously identified these genes. Here, we present Housekeeping Transcript Atlas (HRT Atlas v1.0, www.housekeeping.unicamp.br) a web-based database which addresses some of the previously observed limitations in the identification of these genes, and offers a more accurate database of human and mouse HK genes and transcripts. The database was generated by mining massive human and mouse RNA-seq data sets, including 12,482 and 507 high-quality RNA-seq samples from 82 human non-disease tissues/cells and 15 healthy tissues/cells of C57BL/6 wild type mouse, respectively. User can visualize the expression and download lists of 2,158 human HK transcripts from 2,176 HK genes and 3,024 mouse HK transcripts from 3,277 mouse HK genes. HRT Atlas also offers the most stable and suitable tissue selective candidate reference transcripts for normalization of qPCR experiments. Specific primers and predicted modifiers of gene expression for some of these HK transcripts are also proposed. HRT Atlas has also been integrated with regulatory elements from Epiregio server. All of these resources can be accessed and downloaded from any computer or small device web browsers.

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SARS-CoV-2 receptor and entry genes are expressed by sustentacular cells in the human olfactory neuroepithelium

10.1101/2020.03.31.013268 ◽

2020 ◽

Cited By ~ 31

Author(s):

Leon Fodoulian ◽

Joel Tuberosa ◽

Daniel Rossier ◽

Madlaina Boillat ◽

Chenda Kan ◽

...

Keyword(s):

Sensory System ◽

Cell Types ◽

Sensory Epithelium ◽

Brain Cell ◽

Rna Seq ◽

Angiotensin Converting Enzyme 2 ◽

Sustentacular Cells ◽

The Brain ◽

Brain Cell Types ◽

Human And Mouse

AbstractVarious reports indicate an association between COVID-19 and anosmia, suggesting an infection of the olfactory sensory epithelium, and thus a possible direct virus access to the brain. To test this hypothesis, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2), and for the virus internalization enhancer TMPRSS2. We analyzed a human olfactory single-cell RNA-seq dataset and determined that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express ACE2 and TMPRSS2. We then observed that the ACE2 protein was highly expressed in a subset of sustentacular cells in human and mouse olfactory tissues. Finally, we found ACE2 transcripts in specific brain cell types, both in mice and humans. Sustentacular cells thus represent a potential entry door for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain.

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Increased DAAM2, a new podocyte-associated protein, in diabetic nephropathy

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab014 ◽

2021 ◽

Author(s):

Chenyang Qi ◽

Faten Al Somali ◽

Jinyong Zhong ◽

Raymond C Harris ◽

Valentina Kon ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Cell Function ◽

Enzyme Inhibitor ◽

Normal Donor ◽

Rna Seq ◽

Dipeptidyl Peptidase 4 ◽

Dipeptidyl Peptidase 4 Inhibitor ◽

Glomerular Size ◽

Normal Human ◽

Human And Mouse

Abstract Background Previously, by using proteomic analysis and RNA-seq in isolated glomeruli, we identified several novel differentially expressed proteins in human and mouse diabetic nephropathy (DN) vs control, including DAAM2. DAAM2, the disheveled associated activator of morphogenesis 2 protein, binds the Wnt effector Disheveled. We now aimed to study possible contributions of DAAM2 to DN. Methods We assessed DAAM2 by immunostaining in non-cancer regions of human nephrectomy (Nx), DN and normal donor kidney tissues. We also examined DAAM2 in DN mice (db/db/eNOS-/-) and Nx mice. DN mice treated with angiotensin converting enzyme inhibitor (ACEI) or dipeptidyl peptidase 4 inhibitor (DPP4I) or vehicle were compared. DAAM2 was knocked down in primary cultured podocytes by siRNA to study its effects on cell function. Results In normal human glomeruli, DAAM2 was expressed only on podocytes. DAAM2 expression was increased in both Nx and DN vs normal donors. Podocyte DAAM2 expression was increased in DN and Nx mouse models. Glomerular DAAM2 expression correlated with glomerular size and was decreased significantly by ACEI, while DPP4I only numerically reduced DAAM2. In primary cultured podocytes, knock down of DAAM2 enhanced adhesion, slowed migration, activated Wnt/β-catenin signaling and downregulated mTORC1 and Rho activity. Conclusions Podocyte DAAM2 is upregulated in both nephrectomy and DN, which could be contributed to by glomerular hypertrophy. We hypothesize that DAAM2 regulates podocyte function through the mTORC1, Wnt/β-catenin and Rho signaling pathways.

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microRNAs Regulating Human and Mouse Naïve Pluripotency

International Journal of Molecular Sciences ◽

10.3390/ijms20235864 ◽

2019 ◽

Vol 20 (23) ◽

pp. 5864 ◽

Cited By ~ 3

Author(s):

Yuliang Wang ◽

Abdiasis M. Hussein ◽

Logeshwaran Somasundaram ◽

Rithika Sankar ◽

Damien Detraux ◽

...

Keyword(s):

Cell Fate ◽

Target Genes ◽

Meta Analysis ◽

Regulation Of Gene Expression ◽

Developmental Pathways ◽

State Transitions ◽

Rna Seq ◽

Non Coding Rnas ◽

Post Transcriptional Regulation ◽

Human And Mouse

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.

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HRT Atlas v1.0 database: redefining human and mouse housekeeping genes and candidate reference transcripts by mining massive RNA-seq datasets

Nucleic Acids Research ◽

10.1093/nar/gkaa609 ◽

2020 ◽

Cited By ~ 3

Author(s):

Bidossessi Wilfried Hounkpe ◽

Francine Chenou ◽

Franciele de Lima ◽

Erich Vinicius De Paula

Keyword(s):

Gene Expression ◽

Wild Type Mouse ◽

Housekeeping Genes ◽

Regulatory Elements ◽

Data Sets ◽

Rna Seq ◽

Cellular Functions ◽

Evolutionary Features ◽

Reference Transcript ◽

Human And Mouse

Abstract Housekeeping (HK) genes are constitutively expressed genes that are required for the maintenance of basic cellular functions. Despite their importance in the calibration of gene expression, as well as the understanding of many genomic and evolutionary features, important discrepancies have been observed in studies that previously identified these genes. Here, we present Housekeeping and Reference Transcript Atlas (HRT Atlas v1.0, www.housekeeping.unicamp.br) a web-based database which addresses some of the previously observed limitations in the identification of these genes, and offers a more accurate database of human and mouse HK genes and transcripts. The database was generated by mining massive human and mouse RNA-seq data sets, including 11 281 and 507 high-quality RNA-seq samples from 52 human non-disease tissues/cells and 14 healthy tissues/cells of C57BL/6 wild type mouse, respectively. User can visualize the expression and download lists of 2158 human HK transcripts from 2176 HK genes and 3024 mouse HK transcripts from 3277 mouse HK genes. HRT Atlas also offers the most stable and suitable tissue selective candidate reference transcripts for normalization of qPCR experiments. Specific primers and predicted modifiers of gene expression for some of these HK transcripts are also proposed. HRT Atlas has also been integrated with a regulatory elements resource from Epiregio server.

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