scholarly journals Temporal proteomic profiling of postnatal human cortical development

2017 ◽  
Author(s):  
Michael S. Breen ◽  
Sureyya Ozcan ◽  
Jordan M. Ramsey ◽  
Zichen Wang ◽  
Avi Ma’ayan ◽  
...  
Keyword(s):  
Protein Expression ◽  
Developmental Trajectories ◽  
Expression Profiles ◽  
Cortical Development ◽  
Postnatal Life ◽  
Regulation Of Transcription ◽  
Transcriptome Data ◽  
Proteomic Profiling ◽  
Data Resource ◽  
Age Related

AbstractHealthy cortical development depends on precise regulation of transcription and translation. However, the dynamics of how proteins are expressed, function and interact across postnatal human cortical development remain poorly understood. We surveyed the proteomic landscape of 69 dorsolateral prefrontal cortex samples across seven stages of postnatal life and integrated these data with paired transcriptome data. We detected 911 proteins by liquid chromatography-mass spectrometry, and 83 were significantly associated with postnatal age (FDR p < 0.05). Network analysis identified three modules of co-regulated proteins correlated with age, including two modules with increasing expression involved in gliogenesis and NADH-metabolism and one neurogenesis-related module with decreasing expression throughout development. Integration with paired transcriptome data revealed that these age-related protein modules overlapped with RNA modules and displayed collinear developmental trajectories. Importantly, RNA expression profiles that are dynamically regulated throughout cortical development display tighter correlations with their respective translated protein expression compared to those RNA profiles that are not. Moreover, the correspondence between RNA and protein expression significantly decreases as a function of cortical aging, especially for genes involved in myelination and cytoskeleton organization. Finally, we used this data resource to elucidate the functional impact of genetic risk loci for intellectual disability, converging on gliogenesis, myelination and ATP-metabolism modules in the proteome and transcriptome. We share all data in an interactive, searchable companion website. Collectively, our findings reveal dynamic aspects of protein regulation and provide new insights into brain development, maturation and disease.

Cytokine Profiling of Acute Meylogenous Leukemia and Myelodysplasia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2355-2355
Author(s):  
Steven M. Kornblau ◽  
David McCue ◽  
Kang L. Lu ◽  
Wenjing Chen ◽  
Kevin R. Coombes
Keyword(s):  
Protein Expression ◽  
Expression Profiles ◽  
Pearson Correlation ◽  
Expression Patterns ◽  
Myelogenous Leukemia ◽  
High Expression ◽  
Leukemic Cells ◽  
Proteomic Profiling ◽  
Serum Samples ◽  
Average Linkage

Abstract Protein expression and activation determines the pathophysiology of leukemic cells in Myelodysplasia (MDS) and Acute Myelogenous Leukemia (AML) and is dependent on endogenous changes (e.g mutation, methylation) and exogenous signals from stromal interactions, cytokines (CTKN) and chemokines. We have previously performed proteomics on primary AML sample (using reverse phase protein arrays) and wanted to assess how cytokines affect protein expression and phosphorylation. Prior studies of CTKN expression in AML and MDS have generally measured individual CTKNs, but not provided an overall assessment of CTKN expression. We measured the level of 26 CTKN (IL-1RA, 1B, 2, 4 5, 6, 7 , 8 , 9, 10,12, 13, 15, 17, Eotaxin, FGFB, G-CSF, GM-CSF, IFNγ, IP10, MCP1, MIP1α, MIP1β, PDGF, TNFα and VEGF) using multiplex cytometry (Bioplex™, Biorad) in serum samples from 176 AML (138 untreated (New), 38 relapsed (REL)) and 114 MDS patients (97 New, 10 post biological therapy, 7 REL) and 19 normal (NL) subjects. Individual CTKN expression was not correlated with clinical features (e.g. age, gender, cytogenetics, FAB, HB, WBC, platelet etc). The levels of IL -1β, 4, 5, 6, 7,10,12, 13, 17, IFNγ, FGFB and MIP1α were significantly lower and IL-8 and 15 higher in AML/MDS compared to NL. The expression profiles of AML and MDS were statistically indistinguishable whether analyzed individually or by unsupervised hierarchical clustering, except for IL-8 and 13 (higher in AML) and VEGF (higher in MDS). When CTKN were evaluated individually in new AML cases higher levels of IL4, 5 and 10 correlated significantly with remission attainment, and higher levels of IL8, Il1Ra, IP-10, Mip1β, VEGF and ILR, correlated significantly with shorter survival. No CTKN predicted remission attainment or survival in MDS. Unsupervised hierarchical bootstrap clustering using Pearson correlation and average linkage of CTKN expression relative to other CTKN expression, where high levels of one CTKN correlated with high expression of the other, revealed 6 highly reproducible expression patterns: IL-1β 4, 7, 10, 12, 13, G-CSF, IFNγ, MIP1α and PDGF IL 1ra, 6, 8 Eotaxin, IP-10, MIP1β and VEGF, IL2, 9, 15 and GMCSF, IL5 IL-7, FGF-Basic, TNFα and MCP1. Similar unsupervised clustering of the samples based on CTKN expression using average linkage also revealed 5 disease clusters and a NL sample cluster (containing all 19 NL samples). Average expression levels of each CTKN in these 5 clusters show diminished expression of most CTKN that had high expression in the NL samples, with each group showing increase in expression in a distinct subset of CTKN relative to NL. Remission attainment was strongly associated with cytokine signature (P=0.005). Additional CTKN are being studied (SCF, TGFβ, IL3). Comparison of CTKN expression patterns with proteomic profiling of expression and phosphorylation status is pending. In summary, this is the largest sample set studied for multiple CTKN expression in AML and MDS and the first assessment of many of these CTKN in these diseases. Most CTKNs showed different expression in AML and MDS compared to NL. Interestingly, CTKN expression in AML and MDS were similar. Many CTKN are predictive of outcome individually. CTKN signatures distinguish groups of patients and are predictive of outcome. Correlation with proteomic profiling may suggest CTKN to target in combination with other targeted therapies to maximally affect activated pathways.

Comparative proteomic profiling of Hodgkin lymphoma cell lines

2016 ◽  
Vol 12 (1) ◽  
pp. 219-232 ◽  
Author(s):  
D. Vergara ◽  
P. Simeone ◽  
S. De Matteis ◽  
S. Carloni ◽  
P. Lanuti ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lines ◽  
Expression Profiles ◽  
Lymphoma Cell ◽  
Classical Hodgkin Lymphoma ◽  
Proteomic Profiling ◽  
Hodgkin Lymphoma Cell ◽  
Protein Expression Profiles

Classical Hodgkin lymphoma models of T- and B-cell derivation show significant differences in their protein expression profiles.

scholarly journals Temporal Profiling of the Cortical Synaptic Mitochondrial Proteome Identifies Ageing Associated Regulators of Stability

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3403
Author(s):  
Laura C. Graham ◽  
Rachel A. Kline ◽  
Douglas J. Lamont ◽  
Thomas H. Gillingwater ◽  
Neil A. Mabbott ◽  
...  
Keyword(s):  
Protein Expression ◽  
Expression Profiles ◽  
Mitochondrial Protein ◽  
Wild Type Mouse ◽  
Proteomic Profiling ◽  
Temporal Regulation ◽  
Mitochondrial Proteome ◽  
Age Dependent ◽  
Protein Expression Profiles

Synapses are particularly susceptible to the effects of advancing age, and mitochondria have long been implicated as organelles contributing to this compartmental vulnerability. Despite this, the mitochondrial molecular cascades promoting age-dependent synaptic demise remain to be elucidated. Here, we sought to examine how the synaptic mitochondrial proteome (including strongly mitochondrial associated proteins) was dynamically and temporally regulated throughout ageing to determine whether alterations in the expression of individual candidates can influence synaptic stability/morphology. Proteomic profiling of wild-type mouse cortical synaptic and non-synaptic mitochondria across the lifespan revealed significant age-dependent heterogeneity between mitochondrial subpopulations, with aged organelles exhibiting unique protein expression profiles. Recapitulation of aged synaptic mitochondrial protein expression at the Drosophila neuromuscular junction has the propensity to perturb the synaptic architecture, demonstrating that temporal regulation of the mitochondrial proteome may directly modulate the stability of the synapse in vivo.

Temporal Proteomic Profiling During Differentiation of Normal and Dystrophin-Deficient Human Muscle Cells

2021 ◽  
pp. 1-18
Author(s):  
Mansi V. Goswami ◽  
Shefa M. Tawalbeh ◽  
Emily H. Canessa ◽  
Yetrib Hathout
Keyword(s):  
Protein Expression ◽  
Muscle Development ◽  
Expression Profiles ◽  
Temporal Changes ◽  
Myoblast Differentiation ◽  
Proteomic Profiling ◽  
Proteome Profiling ◽  
Proteome Discoverer ◽  
Attractive Therapeutic Target ◽  
Major Alteration

Background: Myogenesis is a dynamic process involving temporal changes in the expression of many genes. Lack of dystrophin protein such as in Duchenne muscular dystrophy might alter the natural course of gene expression dynamics during myogenesis. Objective: To gain insight into the dynamic temporal changes in protein expression during differentiation of normal and dystrophin deficient myoblasts to myotubes. Method: A super SILAC spike-in strategy in combination and LC-MS/MS was used for temporal proteome profiling of normal and dystrophin deficient myoblasts during differentiation. The acquired data was analyzed using Proteome Discoverer 2.2. and data clustering using R to define significant temporal changes in protein expression. Results: sFour major temporal protein clusters that showed sequential dynamic expression profiles during myogenesis of normal myoblasts were identified. Clusters 1 and 2, consisting mainly of proteins involved mRNA splicing and processing expression, were elevated at days 0 and 0.5 of differentiation then gradually decreased by day 7 of differentiation, then remained lower thereafter. Cluster 3 consisted of proteins involved contractile muscle and actomyosin organization. They increased in their expression reaching maximum at day 7 of differentiation then stabilized thereafter. Cluster 4 consisting of proteins involved in skeletal muscle development glucogenesis and extracellular remodeling had a lower expression during myoblast stage then gradually increased in their expression to reach a maximum at days 11–15 of differentiation. Lack of dystrophin expression in DMD muscle myoblast caused major alteration in temporal expression of proteins involved in cell adhesion, cytoskeleton, and organelle organization as well as the ubiquitination machinery. Conclusion: Time series proteome profiling using super SILAC strategy is a powerful method to assess temporal changes in protein expression during myogenesis and to define the downstream consequences of lack of dystrophin on these temporal protein expressions. Key alterations were identified in dystrophin deficient myoblast differentiation compared to normal myoblasts. These alterations could be an attractive therapeutic target.

scholarly journals Divergent neuronal DNA methylation patterns across human cortical development reveal critical periods and a unique role of CpH methylation

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Amanda J. Price ◽  
Leonardo Collado-Torres ◽  
Nikolay A. Ivanov ◽  
Wei Xia ◽  
Emily E. Burke ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Developmental Trajectories ◽  
Cortical Development ◽  
Postnatal Life ◽  
Critical Periods ◽  
Neuropsychiatric Diseases ◽  
Genome Bisulfite Sequencing ◽  
Highly Correlated ◽  
Genomic Regions ◽  
The Relationship

Abstract Background DNA methylation (DNAm) is a critical regulator of both development and cellular identity and shows unique patterns in neurons. To better characterize maturational changes in DNAm patterns in these cells, we profile the DNAm landscape at single-base resolution across the first two decades of human neocortical development in NeuN+ neurons using whole-genome bisulfite sequencing and compare them to non-neurons (primarily glia) and prenatal homogenate cortex. Results We show that DNAm changes more dramatically during the first 5 years of postnatal life than during the entire remaining period. We further refine global patterns of increasingly divergent neuronal CpG and CpH methylation (mCpG and mCpH) into six developmental trajectories and find that in contrast to genome-wide patterns, neighboring mCpG and mCpH levels within these regions are highly correlated. We integrate paired RNA-seq data and identify putative regulation of hundreds of transcripts and their splicing events exclusively by mCpH levels, independently from mCpG levels, across this period. We finally explore the relationship between DNAm patterns and development of brain-related phenotypes and find enriched heritability for many phenotypes within identified DNAm features. Conclusions By profiling DNAm changes in NeuN-sorted neurons over the span of human cortical development, we identify novel, dynamic regions of DNAm that would be masked in homogenate DNAm data; expand on the relationship between CpG methylation, CpH methylation, and gene expression; and find enrichment particularly for neuropsychiatric diseases in genomic regions with cell type-specific, developmentally dynamic DNAm patterns.

HEPATIC TRANSPORTER PROTEIN EXPRESSION IN FETUSES, NEONATES AND YOUNG INFANTS

2015 ◽  
Vol 101 (1) ◽  
pp. e1.23-e1
Author(s):  
Miriam Mooij ◽  
Evita Van de Steeg ◽  
Heleen Wortelboer ◽  
Wouter Vaes ◽  
Dick Tibboel ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Gestational Age ◽  
Expression Profiles ◽  
Age Groups ◽  
Developmental Expression ◽  
Transporter Protein ◽  
Young Infants ◽  
Age Related ◽  
Hepatic Transporters

BackgroundTransporters are membrane-bound proteins involved in trafficking substrates (e.g. drugs) across membranes of among others hepatocytes. Limited data exists on the developmental expression. We aim to study protein expression of transporters in fetal, neonatal and infantile liver.MethodsTransporter protein expression (ABCB1, ABCG2, ABCC2, ABCC3, BSEP, GLUT1, MCT1, OATP1B1, OATP2B1, OCTN2) was quantified using UPLC-MS-MS, on snap-frozen post mortem livers (Erasmus MC tissuebank) and adult control livers (UMC-Groningen). Protein expression was determined in isolated crude membrane and quantified using stable-isotope-labelled peptides. Age groups were compared with Mann-Whitney test and post hoc Bonferroni-correction (significance p<0.05). Data was compared to mRNA expression.Results25 liver samples were studied. 10 fetal [median gestational age 23.2 weeks (range 16.4–37.9)], 12 pediatric [postnatal age 1 week (0–11.4) and gestational age at birth 35.1 weeks (27.1–41.0)], and 3 adult liver samples. ABCB1, ABCC2, OATP1B1, OATP2B1 expressions appeared similar in fetuses, pediatrics and adults. MCT1 expression was similar in fetuses and adults, but higher in pediatrics. BSEP expression was lower in fetuses and pediatrics than in adults. ABCC3 expression was lower level in fetuses than in adults, but not in pediatrics compared to adults. ABCG2, GLUT1, OCTN2 expressions were higher in fetuses than in adults, but similar in pediatrics and adults.ConclusionHepatic transporters appear in different developmental expression profiles. ABCB1, ABCC2, OATP1B1 protein expression appears stable. This contrast previous mRNA expression data, which showed lower expression in fetus/neonate. The age-related differences in transporter expression may result in age-dependent pharmacokinetics of substrates.

scholarly journals Honeysuckle Aqueous Extracts Induced let-7a Suppress EV71 Replication and Pathogenesis In Vitro and In Vivo and Is Predicted to Inhibit SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 308
Author(s):  
Ying-Ray Lee ◽  
Chia-Ming Chang ◽  
Yuan-Chieh Yeh ◽  
Chi-Ying F. Huang ◽  
Feng-Mao Lin ◽  
...  
Keyword(s):  
Protein Expression ◽  
Western Blotting ◽  
Expression Profiles ◽  
Plaque Assay ◽  
Virus Titer ◽  
Enterovirus 71 ◽  
Luciferase Reporter ◽  
Pathogen Invasion

Honeysuckle (Lonicera japonica Thunb) is a traditional Chinese medicine (TCM) with an antipathogenic activity. MicroRNAs (miRNAs) are small non-coding RNA molecules that are ubiquitously expressed in cells. Endogenous miRNA may function as an innate response to block pathogen invasion. The miRNA expression profiles of both mice and humans after the ingestion of honeysuckle were obtained. Fifteen overexpressed miRNAs overlapped and were predicted to be capable of targeting three viruses: dengue virus (DENV), enterovirus 71 (EV71) and SARS-CoV-2. Among them, let-7a was examined to be capable of targeting the EV71 RNA genome by reporter assay and Western blotting. Moreover, honeysuckle-induced let-7a suppression of EV71 RNA and protein expression as well as viral replication were investigated both in vitro and in vivo. We demonstrated that let-7a targeted EV71 at the predicted sequences using luciferase reporter plasmids as well as two infectious replicons (pMP4-y-5 and pTOPO-4643). The suppression of EV71 replication and viral load was demonstrated in two cell lines by luciferase activity, RT-PCR, real-time PCR, Western blotting and plaque assay. Furthermore, EV71-infected suckling mice fed honeysuckle extract or inoculated with let-7a showed decreased clinical scores and a prolonged survival time accompanied with decreased viral RNA, protein expression and virus titer. The ingestion of honeysuckle attenuates EV71 replication and related pathogenesis partially through the upregulation of let-7a expression both in vitro and in vivo. Our previous report and the current findings imply that both honeysuckle and upregulated let-7a can execute a suppressive function against the replication of DENV and EV71. Taken together, this evidence indicates that honeysuckle can induce the expression of let-7a and that this miRNA as well as 11 other miRNAs have great potential to prevent and suppress EV71 replication.

scholarly journals Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Katherine R. Dobbs ◽  
Paula Embury ◽  
Emmily Koech ◽  
Sidney Ogolla ◽  
Stephen Munga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Young Adults ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Inflammatory Gene Expression ◽  
Cpg Sites ◽  
Age Related ◽  
Adults And Children

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

scholarly journals BART Cancer: a web resource for transcriptional regulators in cancer genomes

NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Zachary V Thomas ◽  
Zhenjia Wang ◽  
Chongzhi Zang
Keyword(s):  
Gene Expression ◽  
Cancer Research ◽  
Computational Prediction ◽  
Transcriptional Regulators ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Regulation Of Transcription ◽  
Data Resource ◽  
Web Resource ◽  
Cancer Types

Abstract Dysregulation of gene expression plays an important role in cancer development. Identifying transcriptional regulators, including transcription factors and chromatin regulators, that drive the oncogenic gene expression program is a critical task in cancer research. Genomic profiles of active transcriptional regulators from primary cancer samples are limited in the public domain. Here we present BART Cancer (bartcancer.org), an interactive web resource database to display the putative transcriptional regulators that are responsible for differentially regulated genes in 15 different cancer types in The Cancer Genome Atlas (TCGA). BART Cancer integrates over 10000 gene expression profiling RNA-seq datasets from TCGA with over 7000 ChIP-seq datasets from the Cistrome Data Browser database and the Gene Expression Omnibus (GEO). BART Cancer uses Binding Analysis for Regulation of Transcription (BART) for predicting the transcriptional regulators from the differentially expressed genes in cancer samples compared to normal samples. BART Cancer also displays the activities of over 900 transcriptional regulators across cancer types, by integrating computational prediction results from BART and the Cistrome Cancer database. Focusing on transcriptional regulator activities in human cancers, BART Cancer can provide unique insights into epigenetics and transcriptional regulation in cancer, and is a useful data resource for genomics and cancer research communities.

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