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Transcriptomics in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 17669

Special Issue Editor


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Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Interests: bioinformatics; multi-omics; transcriptomics;translational research; biomarkers; multidrug resistance; inflammatory skin diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Transcriptomics technologies are the techniques used to study an organism's transcriptome, the sum of all of its RNA transcripts. The information content of an organism is recorded in the DNA of its genome and expressed through transcription. Here, mRNA serves as a transient intermediary molecule in the information network, whilst non-coding RNAs perform additional diverse functions.

Since the late 1990s, transcriptomics has become a widely used discipline in the biological sciences. There are two key contemporary technologies in the field: microarray, which quantifies a set of predetermined sequences; and RNA-Seq, which uses high-throughput sequencing to document all transcripts. Measuring the expression of an organism's genes in different tissues or conditions, or at different times, can provide information about how genes are regulated and reveal details about an organism's biology. It can also be used to infer the function of previously unannotated genes. Transcriptome analysis enables the study of changes in gene expression in different organisms and contributes to the understanding of human disease.

This Special Issue will focus on the molecular research of transcriptomic techniques in health and disease, with particular emphasis on emerging single-cell RNA-seq and spatial transcriptomics.

Prof. Dr. Thomas Litman
Guest Editor

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Keywords

  • transcriptomics
  • RNA-seq data analysis
  • RNA editing
  • RNA modifications
  • single-cell RNA-seq
  • spatial transcriptomics

Published Papers (5 papers)

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Research

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18 pages, 4346 KiB  
Article
Integrated Analysis of Transcriptome and Metabolome Provides Insight into Camellia oleifera Oil Alleviating Fat Accumulation in High-Fat Caenorhabditis elegans
by Li Liu, Qingbo Kong, Zhuoya Xiang, Xuekun Kuang, Heng Wang, Lijun Zhou, Shiling Feng, Tao Chen and Chunbang Ding
Int. J. Mol. Sci. 2023, 24(14), 11615; https://doi.org/10.3390/ijms241411615 - 19 Jul 2023
Cited by 2 | Viewed by 1307
Abstract
Camellia oil (CO) is a high medicinal and nutritional value edible oil. However, its ability to alleviate fat accumulation in high-fat Caenorhabditis elegans has not been well elucidated. Therefore, this study aimed to investigate the effect of CO on fat accumulation in high-fat [...] Read more.
Camellia oil (CO) is a high medicinal and nutritional value edible oil. However, its ability to alleviate fat accumulation in high-fat Caenorhabditis elegans has not been well elucidated. Therefore, this study aimed to investigate the effect of CO on fat accumulation in high-fat C. elegans via transcriptome and metabolome analysis. The results showed that CO significantly reduced fat accumulation in high-fat C. elegans by 10.34% (Oil Red O method) and 11.54% (TG content method), respectively. Furthermore, CO primarily altered the transcription levels of genes involved in longevity regulating pathway. Specifically, CO decreased lipid storage in high-fat C. elegans by inhibiting fat synthesis. In addition, CO supplementation modulated the abundance of metabolic biomarkers related to pyrimidine metabolism and riboflavin metabolism. The integrated transcriptome and metabolome analyses indicated that CO supplementation could alleviate fat accumulation in high-fat C. elegans by regulating retinol metabolism, drug metabolism—cytochrome P450, metabolism of xenobiotics by cytochrome P450, ascorbate and aldarate metabolism, and pentose and glucuronate interconversions. Overall, these findings highlight the potential health benefits of CO that could potentially be used as a functional edible oil. Full article
(This article belongs to the Special Issue Transcriptomics in Health and Disease)
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23 pages, 8997 KiB  
Article
Pleomorphic Variants of Borreliella (syn. Borrelia) burgdorferi Express Evolutionary Distinct Transcriptomes
by Nina Čorak, Sirli Anniko, Christina Daschkin-Steinborn, Viktoria Krey, Sara Koska, Momir Futo, Tin Široki, Innokenty Woichansky, Luka Opašić, Domagoj Kifer, Anja Tušar, Horst-Günter Maxeiner, Mirjana Domazet-Lošo, Carsten Nicolaus and Tomislav Domazet-Lošo
Int. J. Mol. Sci. 2023, 24(6), 5594; https://doi.org/10.3390/ijms24065594 - 15 Mar 2023
Viewed by 2805
Abstract
Borreliella (syn. Borrelia) burgdorferi is a spirochete bacterium that causes tick-borne Lyme disease. Along its lifecycle B. burgdorferi develops several pleomorphic forms with unclear biological and medical relevance. Surprisingly, these morphotypes have never been compared at the global transcriptome level. To fill [...] Read more.
Borreliella (syn. Borrelia) burgdorferi is a spirochete bacterium that causes tick-borne Lyme disease. Along its lifecycle B. burgdorferi develops several pleomorphic forms with unclear biological and medical relevance. Surprisingly, these morphotypes have never been compared at the global transcriptome level. To fill this void, we grew B. burgdorferi spirochete, round body, bleb, and biofilm-dominated cultures and recovered their transcriptomes by RNAseq profiling. We found that round bodies share similar expression profiles with spirochetes, despite their morphological differences. This sharply contrasts to blebs and biofilms that showed unique transcriptomes, profoundly distinct from spirochetes and round bodies. To better characterize differentially expressed genes in non-spirochete morphotypes, we performed functional, positional, and evolutionary enrichment analyses. Our results suggest that spirochete to round body transition relies on the delicate regulation of a relatively small number of highly conserved genes, which are located on the main chromosome and involved in translation. In contrast, spirochete to bleb or biofilm transition includes substantial reshaping of transcription profiles towards plasmids-residing and evolutionary young genes, which originated in the ancestor of Borreliaceae. Despite their abundance the function of these Borreliaceae-specific genes is largely unknown. However, many known Lyme disease virulence genes implicated in immune evasion and tissue adhesion originated in this evolutionary period. Taken together, these regularities point to the possibility that bleb and biofilm morphotypes might be important in the dissemination and persistence of B. burgdorferi inside the mammalian host. On the other hand, they prioritize the large pool of unstudied Borreliaceae-specific genes for functional characterization because this subset likely contains undiscovered Lyme disease pathogenesis genes. Full article
(This article belongs to the Special Issue Transcriptomics in Health and Disease)
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17 pages, 3609 KiB  
Article
Influence of Butyrate on Impaired Gene Expression in Colon from Patients with High Blood Pressure
by Jing Li, Elaine M. Richards, Eileen M. Handberg, Carl J. Pepine, Eyad Alakrad, Chris E. Forsmark and Mohan K. Raizada
Int. J. Mol. Sci. 2023, 24(3), 2650; https://doi.org/10.3390/ijms24032650 - 31 Jan 2023
Cited by 3 | Viewed by 1937
Abstract
Hypertension (HTN) is associated with gut dysbiosis and the depletion of butyrate-producing bacteria in animal models and people. Furthermore, fecal material transfer from donor hypertensive patients increases blood pressure in normotensive recipient animals and ameliorates HTN-associated pathophysiology. These observations have implications in the [...] Read more.
Hypertension (HTN) is associated with gut dysbiosis and the depletion of butyrate-producing bacteria in animal models and people. Furthermore, fecal material transfer from donor hypertensive patients increases blood pressure in normotensive recipient animals and ameliorates HTN-associated pathophysiology. These observations have implications in the impaired interactions between the gut and gut microbiota in HTN. Although this concept is supported in animal models, little is known about human HTN. Therefore, our objective for this study was to compare gene expression with transcriptomics and its potential to influence microbiota in subjects with normal and high blood pressure (HBP). Colon samples from reference subjects with normal blood pressure (REF) and HBP were used for RNA-seq to analyze their transcriptomes. We observed the significant downregulation of gene sets governing immune responses (e.g., SGK1 and OASL), gut epithelial function (e.g., KRT20 and SLC9A3R1), gut microbiota (e.g., PPARG and CIDEC) and genes associated with cardiovascular and gut diseases (e.g., PLAUR and NLN) in HBP subjects; the expression of genes within these pathways correlated with blood pressure. Potential drug targets in the gut epithelium were identified using the Drug Gene International Database for possible use in HTN. They include peroxisome proliferator-activated receptor gamma (PPRG), active serum/glucocorticoid regulated kinase 1 (SGK1) and 3 beta-hydroxysteroid isomerase type II inhibitor (HSD3B). Finally, butyrate, a microbiota-derived short-chain fatty acid, restored the disrupted expression of certain functional genes in colonic organoids from HBP subjects. Patients with HBP exhibit a unique transcriptome that could underlie impaired gut–microbiota interactions. Targeting these interactions could provide a promising new therapeutic intervention for hypertension management. Full article
(This article belongs to the Special Issue Transcriptomics in Health and Disease)
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13 pages, 3422 KiB  
Article
G-Protein-Coupled Receptors Mediate Modulations of Cell Viability and Drug Sensitivity by Aberrantly Expressed Recoverin 3 within A549 Cells
by Hanae Ichioka, Yoshihiko Hirohashi, Tatsuya Sato, Masato Furuhashi, Megumi Watanabe, Yosuke Ida, Fumihito Hikage, Toshihiko Torigoe and Hiroshi Ohguro
Int. J. Mol. Sci. 2023, 24(1), 771; https://doi.org/10.3390/ijms24010771 - 1 Jan 2023
Cited by 4 | Viewed by 2310
Abstract
To elucidate the currently unknown molecular mechanisms responsible for the aberrant expression of recoverin (Rec) within cancerous cells, we examined two-dimensional (2D) and three-dimensional (3D) cultures of Rec-negative lung adenocarcinoma A549 cells which had been transfected with a plasmid containing human recoverin cDNA [...] Read more.
To elucidate the currently unknown molecular mechanisms responsible for the aberrant expression of recoverin (Rec) within cancerous cells, we examined two-dimensional (2D) and three-dimensional (3D) cultures of Rec-negative lung adenocarcinoma A549 cells which had been transfected with a plasmid containing human recoverin cDNA (A549 Rec) or an empty plasmid as a mock control (A549 MOCK). Using these cells, we measured cytotoxicity by several anti-tumor agents (2D), cellular metabolism including mitochondrial and glycolytic functions by a Seahorse bio-analyzer (2D), the physical properties, size and stiffness of the 3D spheroids, trypsin sensitivities (2D and 3D), and RNA sequencing analysis (2D). Compared with the A549 MOCK, the A549 Rec cells showed (1) more sensitivity toward anti-tumor agents (2D) and a 0.25% solution of trypsin (3D); (2) a metabolic shift from glycolysis to oxidative phosphorylation; and (3) the formation of larger and stiffer 3D spheroids. RNA sequencing analysis and bioinformatic analyses of the differentially expressed genes (DEGs) using Gene Ontology (GO) enrichment analysis suggested that aberrantly expressed Rec is most likely associated with several canonical pathways including G-protein-coupled receptor (GPCR)-mediated signaling and signaling by the cAMP response element binding protein (CREB). The findings reported here indicate that the aberrantly expressed Rec-induced modulation of the cell viability and drug sensitivity may be GPCR mediated. Full article
(This article belongs to the Special Issue Transcriptomics in Health and Disease)
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Review

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18 pages, 15984 KiB  
Review
MicroRNA-Based Diagnosis and Therapy
by Phuong T. B. Ho, Ian M. Clark and Linh T. T. Le
Int. J. Mol. Sci. 2022, 23(13), 7167; https://doi.org/10.3390/ijms23137167 - 28 Jun 2022
Cited by 142 | Viewed by 8025
Abstract
MicroRNAs (miRNAs) are a group of endogenous non-coding RNAs that regulate gene expression. Alteration in miRNA expression results in changes in the profile of genes involving a range of biological processes, contributing to numerous human disorders. With high stability in human fluids, miRNAs [...] Read more.
MicroRNAs (miRNAs) are a group of endogenous non-coding RNAs that regulate gene expression. Alteration in miRNA expression results in changes in the profile of genes involving a range of biological processes, contributing to numerous human disorders. With high stability in human fluids, miRNAs in the circulation are considered as promising biomarkers for diagnosis, as well as prognosis of disease. In addition, the translation of miRNA-based therapy from a research setting to clinical application has huge potential. The aim of the current review is to: (i) discuss how miRNAs traffic intracellularly and extracellularly; (ii) emphasize the role of circulating miRNAs as attractive potential biomarkers for diagnosis and prognosis; (iii) describe how circulating microRNA can be measured, emphasizing technical problems that may influence their relative levels; (iv) highlight some of the circulating miRNA panels available for clinical use; (v) discuss how miRNAs could be utilized as novel therapeutics, and finally (v) update those miRNA-based therapeutics clinical trials that could potentially lead to a breakthrough in the treatment of different human pathologies. Full article
(This article belongs to the Special Issue Transcriptomics in Health and Disease)
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