scholarly journals Transcriptome profiles in brains of mice heterozygous for a DYT1 dystonia-associated mutation in the endogenous Tor1a gene

2019 ◽  
Author(s):  
Sara B. Mitchell ◽  
Michael S. Chimenti ◽  
Hiroyuki Kawano ◽  
Tsun Ming Tom Yuen ◽  
Ashley E. Sjurson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Body Movement ◽  
Gene Expression Profiles ◽  
Brain Regions ◽  
Brain Disorder ◽  
Dyt1 Dystonia ◽  
Differential Gene

ABSTRACTIn patients with the brain disorder dystonia, body movement is severely affected – with involuntary muscle contractions and abnormal postures, causing extensive deterioration of the patient’s quality of life. The most common inherited form of this disorder is DYT1 dystonia, which is caused by a mutation in TOR1A gene and autosomal dominant. The molecular mechanisms that underlie the effects of the TOR1A mutation on brain function remain unclear. To understand these, we examined the gene expression profiles (transcriptome) in four brain regions (cerebral cortex, hippocampus, striatum and cerebellum) in a mouse model, the heterozygous ΔE-torsinA knock-in mice which genetically reproduce the mutation in DYT1 dystonia. The samples were obtained at 2 to 3 weeks of age, a period during which synaptic abnormalities have been reported. Pairwise comparisons of brain regions revealed differential gene expression irrespective of genotype. A comparison of heterozygous to wild-type mice failed to reveal genotype-dependent differences in gene expression in any of the four brain regions when examined individually. However, genotype-dependent differences became apparent when the information for all brain regions was combined. These results suggest that any changes in the transcriptome within a brain region were subtle at this developmental stage, but that statistically significant changes occur across all brain regions. Such changes in the transcriptome, although subtle in degree, could underlie the processes that give rise to DYT1 dystonia.

scholarly journals Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients

2021 ◽  
Vol 14 (1) ◽  
pp. 41
Author(s):  
Hana Votavova ◽  
Zuzana Urbanova ◽  
David Kundrat ◽  
Michaela Dostalova Merkerova ◽  
Martin Vostry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Blood Cell ◽  
Myelodysplastic Syndrome ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Adaptive Immune Response ◽  
Gene Expression Profiles ◽  
Iron Chelator ◽  
Multiple Cancer

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.

PSIV-6 Differential gene expression of fibro/adipogenic progenitors between Wagyu and Brahman cattle: A possible contribution to their different meat quality

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 301-301
Author(s):  
Chaoyang Li ◽  
Qianglin Liu ◽  
Matt Welborn ◽  
Leshan Wang ◽  
Yuxia Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Meat Quality ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cattle Breed ◽  
Intramuscular Fat ◽  
Brahman Cattle ◽  
Differential Gene ◽  
The Difference

Abstract The amount of intramuscular fat directly influences the meat quality. However, significant differences in the ability to accumulate intramuscular fat are present among different beef cattle breeds. While Wagyu, a cattle breed that originated from Japan, is renowned for abundant intramuscular fat, Brahman cattle generally have very little intramuscular fat accumulation and produce tougher meat. We identified that bovine intramuscular fat is derived from a group of bipotent progenitor cells named fibro/adipogenic progenitors (FAPs) which also give rise to fibroblasts. Thus, the variation in intramuscular fat development between Wagyu and Brahman is likely attributed to the difference in FAPs between these two breeds. In order to understand the gene expression difference between FAPs of the two breeds, single-cell RNA-seq was performed using total single-nucleated cells isolated from the longissimus muscle of young purebred Wagyu, purebred Brahman, and Wagyu-Brahman cross cattle. FAPs constitute the largest single-nucleated cell population in both Wagyu and Brahman skeletal muscle. Multiple subpopulations of FAPs with different gene expression profiles were identified, suggesting that FAP is a heterogeneous population. A unique FAP cluster expressing lower levels of fibrillar collagen and extracellular remodeling enzyme genes but higher levels of select proadipogenic genes was identified exclusively in Wagyu skeletal muscle, which likely contributes to the robust intramuscular adipogenic efficiency of Wagyu FAPs. In conclusion, the difference in the cellular composition and gene expression of FAPs between Wagyu and Brahman cattle likely contribute to their distinct meat quality.

scholarly journals Dynamical consequences of regional heterogeneity in the brain’s transcriptional landscape

2020 ◽  
Author(s):  
Gustavo Deco ◽  
Kevin Aquino ◽  
Aurina Arnatkevičiūtė ◽  
Stuart Oldham ◽  
Kristina Sabaroedin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Brain Regions ◽  
Biophysical Model ◽  
Neuronal Dynamics ◽  
Regional Heterogeneity ◽  
Magnetic Resonance Imaging Mri

AbstractBrain regions vary in their molecular and cellular composition, but how this heterogeneity shapes neuronal dynamics is unclear. Here, we investigate the dynamical consequences of regional heterogeneity using a biophysical model of whole-brain functional magnetic resonance imaging (MRI) dynamics in humans. We show that models in which transcriptional variations in excitatory and inhibitory receptor (E:I) gene expression constrain regional heterogeneity more accurately reproduce the spatiotemporal structure of empirical functional connectivity estimates than do models constrained by global gene expression profiles and MRI-derived estimates of myeloarchitecture. We further show that regional heterogeneity is essential for yielding both ignition-like dynamics, which are thought to support conscious processing, and a wide variance of regional activity timescales, which supports a broad dynamical range. We thus identify a key role for E:I heterogeneity in generating complex neuronal dynamics and demonstrate the viability of using transcriptional data to constrain models of large-scale brain function.

scholarly journals Transcriptome-wide gene expression plasticity in Stipa grandis in response to grazing intensity differences

2020 ◽  
Author(s):  
Zhenhua Dang ◽  
Yuanyuan Jia ◽  
Yunyun Tian ◽  
Jiabin Li ◽  
Yanan Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Grazing Intensity ◽  
Glycolate Oxidase ◽  
Bisphosphate Carboxylase ◽  
Grazing Intensities

Organisms have evolved effective and distinct adaptive strategies to survive. Stipa grandis is one of the widespread dominant species on the typical steppe of the Inner Mongolian Plateau, and is regarded as a suitable species for studying the effects of grazing in this region. Although phenotypic (morphological and physiological) variations in S. grandis in response to long-term grazing have been identified, the molecular mechanisms underlying adaptations and plastic responses remain largely unknown. Accordingly, we performed a transcriptomic analysis to investigate changes in gene expression of S. grandis under four different grazing intensities. A total of 2,357 differentially expressed genes (DEGs) were identified among the tested grazing intensities, suggesting long-term grazing resulted in gene expression plasticity that affected diverse biological processes and metabolic pathways in S. grandis. DEGs were identified that indicated modulation of Calvin–Benson cycle and photorespiration metabolic pathways. The key gene´expression profiles encoding various proteins (e.g., Ribulose-1,5-bisphosphate carboxylase/oxygenase, fructose-1,6-bisphosphate aldolase, glycolate oxidase etc.) involved in these pathways suggest that they may synergistically respond to grazing to increase the resilience and stress tolerance of S. grandis. Our findings provide scientific clues for improving grassland use and protection, and identify important questions to address in future transcriptome studies.

scholarly journals Differential Gene Expression Profiles of Cells from Normal, Traumatic and Idiopathic Scoliotic Discs Identify Molecular Dysregulation in Scoliosis

2016 ◽  
Vol 6 (1_suppl) ◽  
pp. s-0036-1582635-s-0036-1582635 ◽  
Author(s):  
Sibylle Grad ◽  
Ying Zhang ◽  
Olga Rozhnova ◽  
Elena Schelkunova ◽  
Mikhail Mikhailovsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differential Gene

scholarly journals SMC4, CCNB1 and CKS1B as potential targets and new critical biomarkers for the prognosis of human bladder cancer

2021 ◽  
Author(s):  
Hongpeng Fang ◽  
Zhansen Huang ◽  
Xianzi Zeng ◽  
Jiaming Wan ◽  
Jieying Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Expression Omnibus ◽  
Transcriptional Level ◽  
Hub Genes ◽  
Kaplan Meier ◽  
High Form

Abstract Background As a common malignant cancer of the urinary system, the precise molecular mechanisms of bladder cancer remain to be illuminated. The purpose of this study was to identify core genes with prognostic value as potential oncogenes for the diagnosis, prognosis or novel therapeutic targets of bladder cancer. Methods The gene expression profiles GSE3167 and GSE7476 were available from the Gene Expression Omnibus (GEO) database. Next, PPI network was built to filter the hub gene through the STRING database and Cytoscape software and GEPIA and Kaplan-Meier plotter were implemented. Frequency and type of hub genes and sub groups analysis were performed in cBioportal and ULCAN database. Finally,We used RT-qPCR to confirm our results. Results Totally, 251 DEGs were excavated from two datasets in our study. We only founded high expression of SMC4, TYMS, CCNB1, CKS1B, NUSAP1 and KPNA2 was associated with worse outcomes in bladder cancer patients and no matter from the type of mutation or at the transcriptional level of hub genes, the tumor showed a high form of expression. However, only the expression of SMC4,CCNB1and CKS1B remained changed between the cancer and the normal samples in our results of RT-qPCR. Conclusion In conclusion,These findings indicate that the SMC4,CCNB1 and CKS1B may serve as critical biomarkers in the development and poor prognosis.

scholarly journals Convergent evolution of venom gland transcriptomes across Metazoa

2021 ◽  
Author(s):  
Giulia Zancolli ◽  
Maarten Reijnders ◽  
Robert Waterhouse ◽  
Marc Robinson-Rechavi
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Venom Gland ◽  
Bioactive Molecules ◽  
Specific Gene ◽  
Animal Kingdom ◽  
Venom Glands

Animals have repeatedly evolved specialized organs and anatomical structures to produce and deliver a cocktail of potent bioactive molecules to subdue prey or predators: venom. This makes it one of the most widespread convergent functions in the animal kingdom. Whether animals have adopted the same genetic toolkit to evolved venom systems is a fascinating question that still eludes us. Here, we performed the first comparative analysis of venom gland transcriptomes from 20 venomous species spanning the main Metazoan lineages, to test whether different animals have independently adopted similar molecular mechanisms to perform the same function. We found a strong convergence in gene expression profiles, with venom glands being more similar to each other than to any other tissue from the same species, and their differences closely mirroring the species phylogeny. Although venom glands secrete some of the fastest evolving molecules (toxins), their gene expression does not evolve faster than evolutionarily older tissues. We found 15 venom gland specific gene modules enriched in endoplasmic reticulum stress and unfolded protein response pathways, indicating that animals have independently adopted stress response mechanisms to cope with mass production of toxins. This, in turns, activates regulatory networks for epithelial development, cell turnover and maintenance which seem composed of both convergent and lineage-specific factors, possibly reflecting the different developmental origins of venom glands. This study represents the first step towards an understanding of the molecular mechanisms underlying the repeated evolution of one of the most successful adaptive traits in the animal kingdom.

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