L1-associated genomic regions are deleted in somatic cells of the healthy human brain â RNA-Sequencing
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2500
ORGANISM(S): Homo sapiens
SUBMITTER: Jennifer Erwin
PROVIDER: E-MTAB-4830 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The healthy human brain is a mosaic of varied genomes. Long interspersed element-1 (LINE-1 or L1) retrotransposition is known to create mosaicism by inserting L1 sequences into new locations of somatic cell genomes. Using a machine learning-based, single-cell sequencing approach, we discovered that somatic L1-associated variants (SLAVs) are composed of two classes: L1 retrotransposition insertions and retrotransposition-independent L1-associated variants. We demonstrate that a subset of SLAVs comprises somatic deletions generated by L1 endonuclease cutting activity. Retrotransposition-independent rearrangements in inherited L1s resulted in the deletion of proximal genomic regions. These rearrangements were resolved by microhomology-mediated repair, which suggests that L1-associated genomic regions are hotspots for somatic copy number variants in the brain and therefore a heritable genetic contributor to somatic mosaicism. We demonstrate that SLAVs are present in crucial neural genes, such as DLG2 (also called PSD93), and affect 44-63% of cells of the cells in the healthy brain.
| S-EPMC5127747 | biostudies-literature
Project description:Targeted sequencing of L1 elements in post-mortem tissues and single cells
2016-08-28 | E-MTAB-3880 | biostudies-arrayexpress
Project description:Whole genome sequencing of single cells from post mortem human hippocampus
2016-08-28 | E-MTAB-4824 | biostudies-arrayexpress
Project description:Analysis of dopaminergic neuronal gene expression changes by Nurr1 and/or Foxa2 overexpression. Result provides that Foxa2 potentiates Nurr1-induced DA neuronal phenotype gene expression. To identify the syergism of Nurr1 and Foxa2 for developing DA neural precursors, neural precusor cells (NPCs) isolated from embryonic brain were treated control, Nurr1, Foxa2 and Nurr1-Foxa2 retrovirus. After treatment of retroviruses, NPCs were cultrued in N2 media withdrawn mitogen (bFGF, EGF) for differetiation of DA neuron. Total RNA was obtained from NPCs in differentiation day 2.
2014-01-16 | E-GEOD-54086 | biostudies-arrayexpress
Project description:Neural precursor cells (NPCs) are multipotent cells that can generate neurons, astrocytes, and oligodendrocytes in the mammalian central nervous system. Although high mobility group nucleosomal binding domain 1 (HMGN1) was highly expressed in NPCs, its functions in neural development are not fully understood. We performed microarray analysis to examine changes in gene expression between control and HMGN1-overexpressed NPCs. NPCs derived from E11.5 mouse forebrains were infected with control or HMGN1 retrovirus in the presence of fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF). Three days after infection, the virus-infected NPCs were dissociated and seeded on poly-D-lysine -coated dishes, and subsequently the cells were cultured for 1 day without FGF2 and EGF.
2014-09-01 | E-GEOD-57534 | biostudies-arrayexpress
Project description:Neural stem cells (NSCs) and progenitor cells (NPCs) are increasingly appreciated to hold great promise for regenerative medicine to treat CNS injuries and neurodegenerative diseases. However, evidence for effective stimulation of neuronal production from endogenous or transplanted NPCs for cell replacement with small molecules remains limited. To identify novel chemical entities/targets for neurogenesis, we had established a NPC phenotypic screen assay and validated it using known small-molecule neurogenesis inducers. Through screening small molecule libraries with annotated targets, we identified BET bromodomain inhibition as a novel mechanism for enhancing neurogenesis. BET bromodomain proteins, Brd2, Brd3, and Brd4 were found to be downregulated in NPCs upon differentiation, while their levels remain unaltered in proliferating NPCs. Consistent with the pharmacological study using bromodomain selective inhibitor (+)-JQ-1, knockdown of each BET protein resulted in an increase in the number of neurons with simultaneous reduction in both astrocytes and oligodendrocytes. Gene expression profiling analysis demonstrated that BET bromodomain inhibition induced a broad but specific transcription program enhancing directed differentiation of NPCs into neurons while suppressing cell cycle progression and gliogenesis. Together, these results highlight a crucial role of BET proteins as promising epigenetic regulators in NPC development and suggest a therapeutic potential of BET inhibitors in treating CNS injury and neurodegenerative diseases. NPCs were treated with (+)-JQ-1 or inactive enantiomer (-)-JQ-1 at 0.2 μM or 0.5 μM for 12 and 24 hrs in differentiation medium. The experiments were carried out in 3 independent preparations of NPCs (triplicates)
2016-07-24 | E-GEOD-77988 | biostudies-arrayexpress
Project description:The idea that stem cell therapies work only via cell replacement is challenged by the observation of consistent intercellular molecule exchange between the graft and the host. Here we defined a mechanism of cellular signaling by which neural stem/precursor cells (NPCs) communicate with the microenvironment via extracellular vesicles (EVs), and we elucidated its molecular signature and function. We observed cytokine-regulated pathways that sort proteins and mRNAs into EVs. We described induction of interferon gamma (IFN-?) pathway in NPCs exposed to proinflammatory cytokines that is mirrored in EVs. We showed that IFN-? bound to EVs through Ifngr1 activates Stat1 in target cells. Finally, we demonstrated that endogenous Stat1 and Ifngr1 in target cells are indispensable to sustain the activation of Stat1 signaling by EV-associated IFN-?/Ifngr1 complexes. Our study identifies a mechanism of cellular signaling regulated by EV-associated IFN-?/Ifngr1 complexes, which grafted stem cells may use to communicate with the host immune system. polyA RNA profiling of Neural Stem/Progenitor cells (NPCs) cultured in basal/Th1/Th2 conditions, of Exosomes derived from NPCs cultured in basal/Th1/Th2 conditions and of EVs derived from NPCs cultured in Basal/Th1/Th2 conditions. Total RNA was purified using Trizol. Purity and integrity were confirmed by BioAnalyser (Agilent). Paired End library construction and poly-A selection were performed by EASIH (The Eastern Sequence and Informatics Hub, University of Cambridge, Cambridge) according to the Illumina standard protocol. Sequencing was performed by EASIH using Illumina GAII.
2014-09-22 | E-GEOD-33527 | biostudies-arrayexpress
Project description:Congenital human cytomegalovirus (HCMV) infection is one of the leading prenatal causes of mental retardation and congenital deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV has been limited by difficulties in sustaining primary cultures. Neuronal cells derived from human induced pluripotent stem (iPS) cells now provide a novel opportunity to investigate HCMV pathogenesis. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their permissiveness to infection with HCMV strain Ad169. Analysis of iPS cells and nearly pure populations of iPS-derived neural stem cells (NSCs), neuroprogenitor cells (NPCs) and neurons suggests that (i) iPS cells are not permissive to HCMV infection; (ii) Neural stem cells have impaired differentiation when infected by HCMV; (iii) NPCs are fully permissive for HCMV infection; the supernatant from infected neural stem cells and NPCs (but not mock infected cells) induced cytopathic effects in human fibroblasts; (iv) most iPS-derived neurons are not permissive to HCMV infection; and (v) infected neurons have impaired calcium influx in response to glutamate. Our approach offers powerful cellular models to investigate the effect of neurotropic viral agents on human neurodevelopment. Adherent monolayer culture of neural progenitor cells (NPCs) were either infected with HCMV Ad169 in triplicate, with each individual sample harvested separately to provide biological replicates for expression analysis. Infected and mock-infected cells were harvested 24 h p.i. RNA. NPCs were 70-80% confluence.
2013-01-04 | E-GEOD-35295 | biostudies-arrayexpress
Project description:To isolate neuronal progenitor cells (NPCs), forebrains of E13.5 Miz1+/+ or Miz1-delta-POZ embryos were cut in small pieces, digested with trypsin and filtered through sterile gauze. Cells were cultivated in 2:1 DMEM/F12 supplemented with 1xB27 (Life technologies), 20 ng/ul EGF (Biomol), 20 ng/?l basic FGF (Biomol), 1 ug/ml fungizone (Gibco) and Penicillin/Streptomycin (PAA). NPCs were passaged every seven days. RNA expression of different genotypes was compared in sec. and quart. neurospheres.
2013-10-01 | E-MEXP-3883 | biostudies-arrayexpress
Project description:Nucleus pulposus (NP) resides in hypoxic microenvironment due to the avascular structure of intervertebral disc (IVD). Intracellular lactate drives lysine lactylation (Kla) as a newly epigenetic modification. However, the impact of Kla on NPCs remains unknown. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we showed a global lactylome profiling on NPCs cultured in normoxia and hypoxia environment and found that 3510 lactylation sites on 1052 proteins in NPCs on non-histone proteins. Moreover, there are 18 proteins with 129 Kla sites exclusively detected in the normoxia group, and 117 Kla sites in 27 proteins were specific in hypoxia group. Together, our dates reveals that Kla plays an important role in regulating cellular metabolism and may contribute to IDD progression.
2025-05-06 | PXD048244 | Pride