scholarly journals Gene expression profiles of YAP1, TAZ, CRB3, and VDR in familial and sporadic multiple sclerosis among an Iranian population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sheyda Khalilian ◽  
Zohreh Hojati ◽  
Fariba Dehghanian ◽  
Vahid Shaygannejad ◽  
Seyedeh Zahra Hosseini Imani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Nervous System ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Hippo Pathway ◽  
Gene Expression Profiles ◽  
Control Group ◽  
Sporadic Group ◽  
The Hippo Pathway

AbstractAlterations in the regulatory mechanisms that control the process of myelination in the nervous system, may lead to the impaired myelination in the Multiple sclerosis. The Hippo pathway is an important mediator of myelination in the nervous system and might contribute to the pathophysiology of MS. This study examined via qPCR the RNA expression of YAP1, TAZ, and CRB3 as the key effectors of the Hippo pathway and also, VDR in the peripheral blood of 35 sporadic, 37 familial MS patients; and also 34 healthy first-degree relatives of the familial MS patients (HFR) and 40 healthy individuals without a family history of the disease (control). The results showed the increased expression of VDR in the sporadic group, as compared to other groups. There was also an increased expression of TAZ in the familial and HFR groups, as compared to the control group. The familial and sporadic patients displayed a significantly lower level of expression of YAP1 in comparison to the HFR group. The increased expression level in the sporadic patients and control group, as compared to the HFR group, was seen in CRB3. We also assessed different clinical parameters and MRI characteristics of the patients. Overall, these findings suggest that Hippo pathway effectors and also VDR gene may play a potential role in the pathophysiology of the sporadic and familial forms of MS. Confirmation of different gene expression patterns in sporadic and familial MS groups may have obvious implications for the personalization of therapies in the disease.

scholarly journals Revisit the Cellular Transmission and Emerging Techniques in Understanding the Mechanisms of Proteinopathies

2021 ◽  
Vol 15 ◽  
Author(s):  
Jinwen Jiang ◽  
Yu Liu ◽  
Qihui Wu
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Single Cell ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Molecular Taxonomy ◽  
Gene Expression Profiles ◽  
Underlying Mechanism ◽  
Signal Pathways ◽  
Parkinson’S Diseases

Alzheimer’s and Parkinson’s diseases (AD and PD) are amongst top of the prevalent neurodegenerative disease. One-third of PD patients are diagnosed with dementia, a pre-symptom of AD, but the underlying mechanism is elusive. Amyloid beta (Aβ) and α-synuclein are two of the most investigated proteins, whose pathological aggregation and spreading are crucial to the pathogenesis of AD and PD, respectively. Transcriptomic studies of the mammalian central nervous system shed light on gene expression profiles at molecular levels, regarding the complexity of neuronal morphologies and electrophysiological inputs/outputs. In the last decade, the booming of the single-cell RNA sequencing technique helped to understand gene expression patterns, alternative splicing, novel transcripts, and signal pathways in the nervous system at single-cell levels, providing insight for molecular taxonomy and mechanistic targets of the degenerative nervous system. Here, we re-visited the cell-cell transmission mechanisms of Aβ and α-synuclein in mediating disease propagation, and summarized recent single-cell transcriptome sequencing from different perspectives and discussed its understanding of neurodegenerative diseases.

Gene Expression Profiles of CD34+ Cells in Myelodysplastic Syndrome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5078-5078
Author(s):  
Monika Belickova ◽  
Alzbeta Vasikova ◽  
Eva Budinska ◽  
Jaroslav Cermak
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Statistical Testing ◽  
Differentially Expressed ◽  
Control Group ◽  
Regulation Of Transcription ◽  
Cd34 Cells

Abstract Myelodysplatic syndrome (MDS) represents a heterogeneous group of clonal disorders with ineffective hematopoiesis that is characterized by dysplasia and peripheral cytopenia of one or more cell lineages. We studied gene expression profiles in CD34+ cells of 42 MDS patients and 6 healthy controls using Illumina cDNA microarray technology. Nine patients had RA, 7 patients had RCMD, 17 patients had RAEB and 9 had RAEB-T. CD34+ cells were isolated from bone marrow samples using MACS magnetic columns. The quality of total extracted RNA was confirmed with the Agilent Bioanalyzer 2100. 200ng of total RNA was amplified using Illumina RNA amplification kit. cRNA targets were hybridized on the Sentrix HumanRef-8 BeadChips (> 24 000 probes), which were scanned on the Illumina BeadStation 500. The data were pre-processed and normalized by lumi R package designed to preprocess the Illumina microarray data. Normalized data were filtered by detection p-value <0.01, resulting in total number of 10 091 genes. This gene set was tested for differential expression between clinical groups and control group. For this purpose, statistical testing by ANOVA with correction for multiple testing problem by Bayesian thresholding was performed. Additionally, analysis by random-forests (RAFT) was performed. Significant genes from both analyses were merged resulting in 332 differentially expressed genes detected. Out of these, 79 genes showed ≥2.5 fold changes in gene expression between controls and all MDS groups (22 up-regulated and 57 down-regulated). Our findings were confirmed by real-time quantitative PCR for several genes (TaqMan Gene Expression Assays). We used DAVID database to annotate 79 selected genes: 8 of 22 up-regulated genes in MDS patients were recognized to play a role in regulation of transcription (LEO1, E2F6 and several zing finger proteins). A half of these over-expressed genes could not be annotated due to still unknown biological function. Within the set of the down-regulated genes in MDS patients those biological processes were predominantly detected: cell differentiation (KLF4, FOSL2, STK17B, BCL3, SNF1LK, ID2 etc.), response to stress (CXCL12, SMAD7, CYGB, etc.) and cell proliferation (MXD1, OSM, FTH1, KLF10 etc.). In the set of 31 genes with 5 fold decreased expression, we identified 8 genes involved in B-cell development. (VPREB1, VPREB3, CD79A, EBI2, LEF1, CXCL12, CTGF, GALNAC4S-6ST). RAFT analysis was performed also in the set of 332 statistically differentially expressed genes in order to evaluate accuracy of grouping the patients according their diagnosis. We detected strong heterogeneity in gene expression patterns within the MDS patients, especially in the RAEB group reflecting clinical diversity of MDS. Clustering analysis (Spearman correlation) showed that most of the RAEB-2 patients (7 out of 9) were clustered together with REAB-T whereas RAEB-1 clustered with RCMD or RA. These results underline the need of distinguishing RAEB-1 and RAEB-2 diagnosis according to WHO classification system, since their expression profiles are significantly different.

scholarly journals Revisit the Cellular Transmission and Emerging Techniques in Proteinopathies

2021 ◽  
Author(s):  
JIngwen Jiang ◽  
Yu Liu ◽  
Qihui Wu
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Single Cell ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Molecular Taxonomy ◽  
Gene Expression Profiles ◽  
Alpha Synuclein ◽  
Signal Pathways ◽  
Parkinson’S Diseases

Alzheimer’s and Parkinson's diseases (AD and PD) are amongst top of the prevalent neurodegenerative disease. One-third of PD patients are diagnosed with dementia, a pre-symptom of AD, but the underlying mechanism is elusive. Amyloid beta (Aβ) and α-synuclein are two of the most investigated proteins, whose pathological aggregation and spreading are crucial to the pathogenesis of AD and PD, respectively. Transcriptomic studies of the mammalian central nervous system shed light on gene expression profiles at molecular levels, regarding the complexity of neuronal morphologies and electrophysiological inputs/outputs. In the last decade, the booming of the single-cell RNA sequencing technique helped to understand gene expression patterns, alternative splicing, novel transcripts, and signal pathways in the nervous system at single-cell levels, providing insight for molecular taxonomy and mechanistic targets of the degenerative nervous system. Here, we re-visited the cell-cell transmission mechanisms of Aβ and α-synuclein in medi-ating disease propagation, and summarized recent single-cell transcriptome sequencing from different perspectives and discussed its understanding of neurodegenerative diseases.

scholarly journals Lateral rectus muscle differentiation potential in paralytic esotropia patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qing Xia ◽  
Xiangtian Ling ◽  
Zhonghao Wang ◽  
Tao Shen ◽  
Minghao Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Rectus Muscle ◽  
Lateral Rectus ◽  
Control Group ◽  
Differentiation Potential ◽  
Partial Restoration ◽  
Reverse Transcription Pcr ◽  
Lateral Rectus Muscle

Abstract Purpose and background Recently, we found that maximal medial rectus recession and lateral rectus resection in patients with complete lateral rectus paralysis resulted in a partial restoration of abduction. In an attempt to understand some of the mechanisms involved with this effect we examined gene expression profiles of lateral recti from these patients, with our focus being directed to genes related to myogenesis. Materials and methods Lateral recti resected from patients with complete lateral rectus paralysis and those from concomitant esotropia (controls) were collected. Differences in gene expression profiles between these two groups were examined using microarray analysis and quantitative Reverse-transcription PCR (qRT-PCR). Results A total of 3056 differentially expressed genes (DEGs) were identified between these two groups. Within the paralytic esotropia group, 2081 genes were up-regulated and 975 down-regulated. The results of RT-PCR revealed that PAX7, MYOG, PITX1, SIX1 and SIX4 showed higher levels of expression, while that of MYOD a lower level of expression within the paralytic esotropia group as compared with that in the control group (p < 0.05). Conclusion The decreased expression of MYOD in the paralytic esotropia group suggested that extraocular muscle satellite cell (EOMSCs) differentiation processes were inhibited. Whereas the high expression levels of PAX7, SIX1/4 and MYOG, suggested that the EOMSCs were showing an effective potential for differentiation. The stimulation resulting from muscle surgery may induce EOMSCs to differentiate and thus restore abduction function.

scholarly journals Discovering Distinct Patterns in Gene Expression Profiles

2008 ◽  
Vol 5 (2) ◽  
Author(s):  
Li Teng ◽  
Laiwan Chan
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Clustering Methods ◽  
Gene Expressions ◽  
Real Gene ◽  
Large Scale Dataset ◽  
Coexpressed Genes

SummaryTraditional analysis of gene expression profiles use clustering to find groups of coexpressed genes which have similar expression patterns. However clustering is time consuming and could be diffcult for very large scale dataset. We proposed the idea of Discovering Distinct Patterns (DDP) in gene expression profiles. Since patterns showing by the gene expressions reveal their regulate mechanisms. It is significant to find all different patterns existing in the dataset when there is little prior knowledge. It is also a helpful start before taking on further analysis. We propose an algorithm for DDP by iteratively picking out pairs of gene expression patterns which have the largest dissimilarities. This method can also be used as preprocessing to initialize centers for clustering methods, like K-means. Experiments on both synthetic dataset and real gene expression datasets show our method is very effective in finding distinct patterns which have gene functional significance and is also effcient.

CFTR ΔF508 mutation has minimal effect on the gene expression profile of differentiated human airway epithelia

2005 ◽  
Vol 289 (4) ◽  
pp. L545-L553 ◽  
Author(s):  
Joseph Zabner ◽  
Todd E. Scheetz ◽  
Hakeem G. Almabrazi ◽  
Thomas L. Casavant ◽  
Jian Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Large Scale ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Primary Cultures ◽  
Gene Expression Profiles ◽  
Filter Method ◽  
Tissue Destruction ◽  
Airway Epithelia

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial chloride channel regulated by phosphorylation. Most of the disease-associated morbidity is the consequence of chronic lung infection with progressive tissue destruction. As an approach to investigate the cellular effects of CFTR mutations, we used large-scale microarray hybridization to contrast the gene expression profiles of well-differentiated primary cultures of human CF and non-CF airway epithelia grown under resting culture conditions. We surveyed the expression profiles for 10 non-CF and 10 ΔF508 homozygote samples. Of the 22,283 genes represented on the Affymetrix U133A GeneChip, we found evidence of significant changes in expression in 24 genes by two-sample t-test ( P < 0.00001). A second, three-filter method of comparative analysis found no significant differences between the groups. The levels of CFTR mRNA were comparable in both groups. There were no significant differences in the gene expression patterns between male and female CF specimens. There were 18 genes with significant increases and 6 genes with decreases in CF relative to non-CF samples. Although the function of many of the differentially expressed genes is unknown, one transcript that was elevated in CF, the KCl cotransporter (KCC4), is a candidate for further study. Overall, the results indicate that CFTR dysfunction has little direct impact on airway epithelial gene expression in samples grown under these conditions.

scholarly journals Single-cell immune repertoire and transcriptome sequencing reveals that clonally expanded and transcriptionally distinct lymphocytes populate the aged central nervous system in mice

2021 ◽  
Vol 288 (1945) ◽  
pp. 20202793
Author(s):  
Alexander Yermanos ◽  
Daniel Neumeier ◽  
Ioana Sandu ◽  
Mariana Borsa ◽  
Ann Cathrin Waindok ◽  
...  
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
B Cells ◽  
Single Cell ◽  
Somatic Hypermutation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Receptor ◽  
The Central Nervous System

Neuroinflammation plays a crucial role during ageing and various neurological conditions, including Alzheimer's disease, multiple sclerosis and infection. Technical limitations, however, have prevented an integrative analysis of how lymphocyte immune receptor repertoires and their accompanying transcriptional states change with age in the central nervous system. Here, we leveraged single-cell sequencing to simultaneously profile B cell receptor and T cell receptor repertoires and accompanying gene expression profiles in young and old mouse brains. We observed the presence of clonally expanded B and T cells in the central nervous system of aged male mice. Furthermore, many of these B cells were of the IgM and IgD isotypes, and had low levels of somatic hypermutation. Integrating gene expression information additionally revealed distinct transcriptional profiles of these clonally expanded lymphocytes. Our findings implicate that clonally related T and B cells in the CNS of elderly mice may contribute to neuroinflammation accompanying homeostatic ageing.

scholarly journals Comparative transcriptomics identifies differences in the regulation of the floral transition between Arabidopsis and Brassica rapa cultivars

2020 ◽  
Author(s):  
Alexander Calderwood ◽  
Jo Hepworth ◽  
Shannon Woodhouse ◽  
Lorelei Bilham ◽  
D. Marc Jones ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brassica Rapa ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Detailed Comparison ◽  
Developmental Time ◽  
Floral Transition ◽  
Gene Regulatory

AbstractThe timing of the floral transition affects reproduction and yield, however its regulation in crops remains poorly understood. Here, we use RNA-Seq to determine and compare gene expression dynamics through the floral transition in the model species Arabidopsis thaliana and the closely related crop Brassica rapa. A direct comparison of gene expression over time between species shows little similarity, which could lead to the inference that different gene regulatory networks are at play. However, these differences can be largely resolved by synchronisation, through curve registration, of gene expression profiles. We find that different registration functions are required for different genes, indicating that there is no common ‘developmental time’ to which Arabidopsis and B. rapa can be mapped through gene expression. Instead, the expression patterns of different genes progress at different rates. We find that co-regulated genes show similar changes in synchronisation between species, suggesting that similar gene regulatory sub-network structures may be active with different wiring between them. A detailed comparison of the regulation of the floral transition between Arabidopsis and B. rapa, and between two B. rapa accessions reveals different modes of regulation of the key floral integrator SOC1, and that the floral transition in the B. rapa accessions is triggered by different pathways, even when grown under the same environmental conditions. Our study adds to the mechanistic understanding of the regulatory network of flowering time in rapid cycling B. rapa under long days and highlights the importance of registration methods for the comparison of developmental gene expression data.

Spatial Transcriptomics analysis of uterine gene expression in enhancer of Zeste homolog 2 (Ezh2) conditional knockout mice

2021 ◽  
Author(s):  
Ana M Mesa ◽  
Jiude Mao ◽  
Theresa I Medrano ◽  
Nathan J Bivens ◽  
Alexander Jurkevich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Reproductive Organs ◽  
Conditional Knockout ◽  
Estrogen Signaling ◽  
Uterine Epithelial Cell ◽  
Stromal Tissue

Abstract Histone proteins undergo various modifications that alter chromatin structure, including addition of methyl groups. Enhancer of homolog 2 (EZH2), is a histone methyltransferase that methylates lysine residue 27, and thereby, suppresses gene expression. EZH2 plays integral role in the uterus and other reproductive organs. We have previously shown that conditional deletion of uterine EZH2 results in increased proliferation of luminal and glandular epithelial cells, and RNAseq analyses reveal several uterine transcriptomic changes in Ezh2 conditional (c) knockout (KO) mice that can affect estrogen signaling pathways. To pinpoint the origin of such gene expression changes, we used the recently developed spatial transcriptomics (ST) method with the hypotheses that Ezh2cKO mice would predominantly demonstrate changes in epithelial cells and/or ablation of this gene would disrupt normal epithelial/stromal gene expression patterns. Uteri were collected from ovariectomized adult WT and Ezh2cKO mice and analyzed by ST. Asb4, Cxcl14, Dio2, and Igfbp5 were increased, Sult1d1, Mt3, and Lcn2 were reduced in Ezh2cKO uterine epithelium vs. WT epithelium. For Ezh2cKO uterine stroma, differentially expressed key hub genes included Cald1, Fbln1, Myh11, Acta2, and Tagln. Conditional loss of uterine Ezh2 also appears to shift the balance of gene expression profiles in epithelial vs. stromal tissue toward uterine epithelial cell and gland development and proliferation, consistent with uterine gland hyperplasia in these mice. Current findings provide further insight into how EZH2 may selectively affect uterine epithelial and stromal compartments. Additionally, these transcriptome data might provide the mechanistic understanding and valuable biomarkers for human endometrial disorders with epigenetic underpinnings.

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