A42f9d07-b3e4-4117-baee-e8e7443522e0 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001008457 | EGA |
REPOSITORIES: EGA
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Project description:We sought to identify alterations in RNA expression and splicing in human grey matter from the brains of people with Multiple Sclerosis (MS) where we observe mislocalization of the RNA binding protein hnRNP A1. Thus, RNA was extracted from fresh-frozen post-mortem brain samples of three people with MS and compared to RNA extracted from fresh-frozen post-mortem brain samples of three healthy controls by RNAseq. Regions of interest in human grey matter were defined by immunostaining for hnRNP A1 to confirm grey matter regions with hnRNP A1 mislocalization in MS tissue, and grey matter regions with normal hnRNP A1 localization in control tissue, and the same region from an adjacent tissue section was dissected with a razor blade and used for RNA extraction and sequencing.
2024-01-04 | GSE207680 | GEO
Project description:Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by increased inflammation and immune responses, oxidative injury, mitochondrial dysfunction, and iron dyshomeostasis leading to demyelination and axonal damage. In MS, incomplete remyelination results in chronically demyelinated axons and degeneration coinciding with disability. This suggests a failure in the ability to remyelinate in MS, however, the precise underlying mechanisms remain unclear. We aimed to identify proteins whose expression was altered in chronic inactive white matter lesions and periplaque white matter in MS tissue to reveal potential pathogenic mechanisms. Laser capture microdissection coupled to proteomics was used to interrogate spatially preserved changes in formalin-fixed paraffin-embedded brain tissue from chronic MS individuals and controls with no apparent neurological complications. Histopathological maps guided the capture of inactive lesions, periplaque white matter, and cortex from chronic MS individuals along with corresponding white matter and cortex from control tissue. Label free quantitation by liquid chromatography tandem mass spectrometry was used to discover differentially expressed proteins between the various brain regions. In addition to confirming loss of several myelin-associated proteins known to be affected in MS, proteomics analysis of chronic inactive MS lesions revealed alterations in myelin assembly, metabolism, and cytoskeletal organization. Notably, a subset of proteins that were altered in MS white matter indicate altered lipid metabolism. Our findings highlight proteome changes in chronic inactive MS white matter lesions and periplaque white matter, which may be crucial for proper myelinogenesis, bioenergetics, focal adhesions, and cellular function. These findings highlight the importance and feasibility of spatial approaches such as laser capture microdissection-based proteomics analysis of pathologically distinct regions of MS brain tissue. Identification of spatially resolved changes in the proteome of MS brain tissue should aid in the understanding of pathophysiological mechanisms and the development of novel therapies.
2024-08-29 | PXD047800 | Pride
Project description:Utilizing a single nuclei multiomics approach, this study elucidates how enhancing histone lysine crotonylation regulates cell type specific gene expression and chromatin accessibility during memory consolidation.
2024-11-13 | GSE281007 | GEO
Project description:Neurodegenerative diseases affect millions of people worldwide and the presence of various physiological barriers limits the accessibility to the brain and reduces the efficacy of various therapies. Moreover, improving the solubility, stability and release of the drug in specific brain regions and in particular target cells (neuron or microglia), are essential factor to develop an efficient and targeted therapy for the treatment of brain disorders. Extracellular vesicles, nanoparticles and artificial nanovesicles represent a promising tool for contrast brain diseases, thanks to their ability to deliver therapeutic molecules and overcoming the problems mentioned. In this study, for the first time, we generated artificial nanovesicles derived from brain tissue, which were preliminary evaluated as potential brain delivery system. The nanovesicles were produced from myelin extracted from the brain, called Myelin NanoVesicles (MyVes). MyVes produced have an average diameter of 100nm, negative zeta potential, spheroidal morphology, lipids and main proteins of the myelin sheath and exhibit good cytocompatibility. The MyVes, are able to load a drug/molecule and cross a blood brain barrier model, in addition, they targeted specific brain regions, white matter and are able to interact mainly with the microglia cell line. Therefore, we propose MyVes for white matter and microglia targeted delivery as a potential approach to counteract white matter microglia related diseases
2021-12-15 | PXD026282 | Pride
Project description:We performed multiomics analysis; single nucleus RNA-seq (snRNA-seq) combined with ATAC (snATAC-seq) with 10XGenomics Multiome platform to generate cell-type-specific gene expression and chromatin accessibility atlas of the mouse polycystic kidney disease on a time course.
2024-10-02 | GSE268494 | GEO
Project description:Suspended animation (e.g. hibernation, diapause) allows organisms to survive extreme environments. But the mechanisms underlying the evolution of suspended animation states are unknown. The African turquoise killifish has evolved diapause as a form of suspended development to survive the complete drought that occurs every summer. Here, we show that gene duplicates – paralogs – exhibit specialized expression in diapause compared to normal development in the African turquoise killifish. Surprisingly, paralogs with specialized expression in diapause are evolutionarily very ancient and are present even in vertebrates that do not exhibit diapause. To determine if evolution of diapause is due to the regulatory landscape rewiring at ancient paralogs, we assessed chromatin accessibility genome-wide in fish species with or without diapause. This analysis revealed an evolutionary recent increase in chromatin accessibility at very ancient paralogs in African turquoise killifish. The increase in chromatin accessibility is linked to the presence of new binding sites for transcription factors, likely due to de novo mutations and transposable element (TE) insertion. Interestingly, accessible chromatin regions in diapause are enriched for lipid metabolism genes, and our lipidomics studies uncover a striking difference in lipid species in African turquoise killifish diapause, which could be critical for long-term survival. Together, our results show that diapause likely originated by repurposing pre-existing gene programs via recent changes in the regulatory landscape. This work raises the possibility that suspended animation programs could be reactivated in other species for long-term preservation via transcription factor remodeling and suggests a mechanism for how complex adaptations evolve in nature.
2021-08-05 | ST001898 | MetabolomicsWorkbench
Project description:Tissue repair using cell transplantation holds popular appeal. This underlines the need to understand stem cells within the target organ. Our laboratory works on the human brain. Using neurosphere methods, we and others have only been able to passage stem/progenitors a very few times with little expansion of numbers. Now we describe an efficient method for the establishment and propagation of human brain stem cells from whatever tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency markers Sox2 and Oct4 are expressed without artificial induction. For the first time, multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells' behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient's own-derived stem cells. Grey matter and white matter: tissue, stem cells and differentiated cells compared. Total RNA from two brain biopsy sources (grey matter, white matter) from one adult human.
2013-08-19 | E-GEOD-41394 | biostudies-arrayexpress
Project description:We compared the gene expression in post-mortem brain specimen dissected from 2 CADASIL patients with samples from 5 non-affected controls in order to discover genes differentially expressed that could be involved in the development of neuronal damage in SVD. Samples form frontal cortex and white matter and occipital cortex and white matter were used.
2015-03-12 | E-MTAB-3395 | biostudies-arrayexpress
Project description:Chromatin organization is a highly orchestrated process that influences gene expression, in part by modulating access of regulatory factors to DNA and nucleosomes. We found that the chromatin accessibility regulator HMGN1, a target of recurrent DNA copy gains in leukemia, controls myeloid differentiation. HMGN1 amplification was associated with increased accessibility, expression, and histone H3K27 acetylation of loci important for hematopoietic stem cell (HSC) function and AML, such as HoxA cluster genes. In vivo, HMGN1 overexpression was linked to decreased quiescence and increased HSC activity in bone marrow transplantation. HMGN1 overexpression also cooperated with the AML-ETO9a fusion oncoprotein to impair myeloid differentiation and enhance leukemia stem cell (LSC) activity. Inhibition of histone acetyltransferases CBP/p300 relieved the HMGN1-associated differentiation block. These data nominate factors that modulate chromatin accessibility as regulators of HSCs and LSCs and suggest that targeting HMGN1 or its downstream effects on histone acetylation could be therapeutically active in AML.
2020-02-25 | PXD017054 | Pride
Project description:<p>Non-coding regions comprise most of the human genome and harbor a significant fraction of risk alleles for neuropsychiatric diseases, yet their functions remain poorly defined. We created a high-resolution map of non-coding elements involved in human cortical neurogenesis by contrasting chromatin accessibility and gene expression in the germinal zone and cortical plate of the developing cerebral cortex. To obtain a high resolution depiction of chromatin structure and gene expression in developing human fetal cortex, we dissected the post-conception week (PCW) 15-17 human neocortex into two major anatomical divisions to distinguish between proliferating neural progenitors and post mitotic neurons: (1) GZ: the neural progenitor-enriched region encompassing the ventricular zone (VZ), subventricular zone (SVZ), and intermediate zone (IZ) and (2) CP: the neuron-enriched region containing the subplate (SP), cortical plate (CP), and marginal zone (MZ). Tissues were obtained from three independent donors and three to four technical replicates from each tissue were processed for ATAC-seq to define the landscape of accessible chromatin and RNA-seq for genome-wide gene expression profiling.</p>
| phs001438 | dbGaP