Temporal proteomic profiling of postnatal human cortical development.
Ontology highlight
ABSTRACT:
SUBMITTER: Breen MS
PROVIDER: S-EPMC6281671 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
Publications
Temporal proteomic profiling of postnatal human cortical development.
Breen Michael S MS Ozcan Sureyya S Ramsey Jordan M JM Wang Zichen Z Ma'ayan Avi A Rustogi Nitin N Gottschalk Michael G MG Webster Maree J MJ Weickert Cynthia Shannon CS Buxbaum Joseph D JD Bahn Sabine S
Translational psychiatry 20181205 1
Healthy 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 sign ...[more]
Similar Datasets
Project description:Mass spectrometry (MS) analysis of human post-mortem central nervous system (CNS) tissue and induced pluripotent stem cell (iPSC)-based directed differentiations offer complementary avenues to define protein signatures of neurodevelopment. Methodological improvements of formalin-fixed, paraffin-embedded (FFPE) protein isolation now enable widespread proteomic analysis of well-annotated archival tissue samples in the context of development and disease. Here, we utilize a shotgun label-free quantification (LFQ) MS method to profile magnetically enriched human cortical neurons and neural progenitor cells (NPCs) derived from iPSCs. We use these signatures to help define spatiotemporal protein dynamics of developing human FFPE cerebral regions. We show that the use of high resolution Q Exactive mass spectrometers now allow simultaneous quantification of >2700 proteins in a single LFQ experiment and provide sufficient coverage to define novel biomarkers and signatures of NPC maintenance and differentiation. Importantly, we show that this abbreviated strategy allows efficient recovery of novel cytoplasmic, membrane-specific and synaptic proteins that are shared between both in vivo and in vitro neuronal differentiation. This study highlights the discovery potential of non-comprehensive high-throughput proteomic profiling of unfractionated clinically well-annotated FFPE human tissue from a diverse array of development and diseased states.
| S-EPMC5587857 | biostudies-literature
Project description:Certain cognitive deficits in schizophrenia have been linked to dysfunction of prefrontal cortical (PFC) ?-aminobutyric acid (GABA) neurons and appear neurodevelopmental in nature. Since opioids suppress GABA neuron activity, we conducted the first study to determine 1) whether the ? opioid receptor (MOR), ? opioid receptor (DOR), and opioid ligand proenkephalin are altered in the PFC of a large cohort of schizophrenia subjects and 2) the postnatal developmental trajectory in monkey PFC of opioid markers that are altered in schizophrenia. We used quantitative polymerase chain reaction to measure mRNA levels from 42 schizophrenia and 42 matched healthy comparison subjects; 18 monkeys chronically exposed to haloperidol, olanzapine, or placebo; and 49 monkeys aged 1 week-11.5 years. We found higher levels for MOR mRNA (+27%) in schizophrenia but no differences in DOR or proenkephalin mRNAs. Elevated MOR mRNA levels in schizophrenia did not appear to be explained by substance abuse, psychotropic medications, or illness chronicity. Finally, MOR mRNA levels declined through early postnatal development, stabilized shortly before adolescence and increased across adulthood in monkey PFC. In schizophrenia, higher MOR mRNA levels may contribute to suppressed PFC GABA neuron activity and might be attributable to alterations in the postnatal developmental trajectory of MOR signaling.
| S-EPMC3328348 | biostudies-literature
Project description:Melioidosis associated with opportunistic pathogen Burkholderia pseudomallei imparts a huge medical burden in Southeast Asia and Australia. At present there is no available human vaccine that protects against B. pseudomallei infection and antibiotic treatments are limited particularly for drug-resistant strains and bacteria in biofilm forms. Biofilm forming bacteria exhibit phenotypic features drastically different to their planktonic states, often exhibiting a diminished response to antimicrobial therapies. Our earlier work on global profiling of bacterial biofilms using transcriptomics and proteomics revealed transcript-decoupled protein abundance in bacterial biofilms. Here we employed reverse phase liquid chromatography tandem mass spectrometry (LC-MS/MS) to deduce temporal proteomic differences in planktonic and biofilm forms of Burkholderia thailandensis, which is weakly surrogate model of pathogenic B. pseudomallei as sharing a key element in genomic similarity. The proteomic analysis of B. thailandensis in biofilm versus planktonic states revealed that proteome changes support biofilm survival through decreased abundance of metabolic proteins while increased abundance of stress-related proteins. Interestingly, the protein abundance including for the transcription protein TEX, outer periplasmic TolB protein, and the exopolyphosphatase reveal adaption in bacterial biofilms that facilitate antibiotic tolerance through a non-specific mechanism. The present proteomics study of B. thailandensis biofilms provides a global snapshot of protein abundance differences and antimicrobial sensitivities in planktonic and sessile bacteria.
| S-EPMC6482045 | biostudies-literature
Project description:This review aims to discuss (1) the refinement of mammalian visual cortical circuits and the maturation of visual functions they subserve in primary visual cortex (V1) and other visual cortical areas, and (2) existing evidence supporting the notion of differential rates of maturation of visual functions in different species. It is well known that different visual functions and their underlying circuitry mature and attain adultlike characteristics at different stages in postnatal development with varying growth rates. The developmental timecourse and duration of refinement varies significantly both in V1 of various species and among different visual cortical areas; while basic visual functions like spatial acuity mature earlier requiring less time, higher form perception such as contour integration is more complex and requires longer postnatal time to refine. This review will highlight the importance of systematic comparative analysis of the differential rates of refinement of visual circuitry and function as that may help reveal underlying key mechanisms necessary for healthy visual development during infancy and adulthood. This type of approach will help future studies to establish direct links between various developmental aspects of different visual cortical areas in both human and animal models; thus enhancing our understanding of vision related neurological disorders and their potential therapeutic remedies.
| S-EPMC7296053 | biostudies-literature
Project description:Detailed observations of transcriptional, translational and post-translational events in the human brain are essential to improving our understanding of its development, function and vulnerability to disease. Here, we exploited label-free quantitative tandem mass-spectrometry to create an in-depth proteomic survey of regions of the postnatal human brain, ranging in age from early infancy to adulthood. Integration of protein data with existing matched whole-transcriptome sequencing (RNA-seq) from the BrainSpan project revealed varied patterns of protein-RNA relationships, with generally increased magnitudes of protein abundance differences between brain regions compared to RNA. Many of the differences amplified in protein data were reflective of cytoarchitectural and functional variation between brain regions. Comparing structurally similar cortical regions revealed significant differences in the abundances of receptor-associated and resident plasma membrane proteins that were not readily observed in the RNA expression data.
| S-EPMC5894337 | biostudies-literature
Project description:Functional genomics of the Gram-positive model organism Bacillus subtilis reveals valuable insights into basic concepts of cell physiology. In this study, we monitor temporal changes in the proteome, transcriptome and extracellular metabolome of B. subtilis caused by glucose starvation. For proteomic profiling, a combination of in vivo metabolic labelling and shotgun mass spectrometric analysis was carried out for five different proteomic subfractions (cytosolic, integral membrane, membrane, surface and extracellular proteome fraction), leading to the identification of ~52% of the predicted proteome of B. subtilis. Quantitative proteomic and corresponding transcriptomic data were analysed with Voronoi treemaps linking functional classification and relative expression changes of gene products according to their fate in the stationary phase. The obtained data comprise the first comprehensive profiling of changes in the membrane subfraction and allow in-depth analysis of major physiological processes, including monitoring of protein degradation.
| S-EPMC3105300 | biostudies-literature
Project description:The precision in space and time of interactions among multiple cortical sites was evaluated by examining repeating precise spatiotemporal patterns of instances in which cortical currents showed brief amplitude undulations. The amplitudes of the cortical current dipoles were estimated by applying a variant of synthetic aperture magnetometry to magnetoencephalographic (MEG) recordings of subjects tapping to metric auditory rhythms of drum beats. Brief amplitude undulations were detected in the currents by template matching at a rate of 2-3 per second. Their timing was treated as point processes, and precise spatiotemporal patterns were searched for. By randomly teetering these point processes within a time window W, we estimated the accuracy of the timing of these brief amplitude undulations and compared the results with those obtained by applying the same analysis to traces composed of random numbers. The results demonstrated that the timing accuracy of patterns was better than 3 ms. Successful classification of two different cognitive processes based on these patterns suggests that at least some of the repeating patterns are specific to a cognitive process.
| S-EPMC4869482 | biostudies-literature
Project description:Ancient protein analysis provides clues to human life and diseases from ancient times. Here, we performed shotgun proteomics of human archeological bones for the first time, using rib bones from the Hitotsubashi site (AD 1657-1683) in Tokyo, called Edo in ancient times. The output data obtained were analysed using Gene Ontology and label-free quantification. We detected leucocyte-derived proteins, possibly originating from the bone marrow of the rib. Particularly prevalent and relatively high expression of eosinophil peroxidase suggests the influence of infectious diseases. This scenario is plausible, considering the overcrowding and unhygienic living conditions of the Edo city described in the historical literature. We also observed age-dependent differences in proteome profiles, particularly for proteins involved in developmental processes. Among them, alpha-2-HS-glycoprotein demonstrated a strong negative correlation with age. These results suggest that analysis of ancient proteins could provide a useful indicator of stress, disease, starvation, obesity and other kinds of physiological and pathological information.
| S-EPMC5493901 | biostudies-literature
Project description:Methylation is a fundamental mechanism used in Nature to modify the structure and function of biomolecules, including proteins, DNA, RNA, and metabolites. Methyl groups are predominantly installed into biomolecules by a large and diverse class of S-adenosyl methionine (SAM)-dependent methyltransferases (MTs), of which there are ∼200 known or putative members in the human proteome. Deregulated MT activity contributes to numerous diseases, including cancer, and several MT inhibitors are in clinical development. Nonetheless, a large fraction of the human MT family remains poorly characterized, underscoring the need for new technologies to characterize MTs and their inhibitors in native biological systems. Here, we describe a suite of S-adenosyl homocysteine (SAH) photoreactive probes and their application in chemical proteomic experiments to profile and enrich a large number of MTs (>50) from human cancer cell lysates with remarkable specificity over other classes of proteins. We further demonstrate that the SAH probes can enrich MT-associated proteins and be used to screen for and assess the selectivity of MT inhibitors, leading to the discovery of a covalent inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme implicated in cancer and metabolic disorders. The chemical proteomics probes and methods for their utilization reported herein should prove of value for the functional characterization of MTs, MT complexes, and MT inhibitors in mammalian biology and disease.
| S-EPMC5072128 | biostudies-literature
Project description:Development of the brain involves the formation and maturation of numerous synapses. This process requires prominent changes of the synaptic proteome and potentially involves thousands of different proteins at every synapse. To date the proteome analysis of synapse development has been studied sparsely. Here, we analyzed the cortical synaptic membrane proteome of juvenile [postnatal day 9 (P9), P15, P21, P27], adolescent (P35) and different adult ages (P70, P140, P280) of C57Bl6/J mice. Using a quantitative proteomics workflow we quantified 1560 proteins of which 696 showed statistically significant differences over time. Proteins of the presynaptic active-zone and postsynaptic element showed increased levels over time; proteins involved in protein synthesis or neurite outgrowth generally decreased in abundance. In several cases, proteins from a single functional molecular entity, e.g., subunits of the NMDA receptor, showed profound differences in their temporal regulation, which may reflect specific synaptic development features of connectivity, strength and plasticity.
2018-10-26 | PXD004129 | Pride