Single nucleus RNA-Seq is not suitable for detection of microglial activation genes in humans
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA644127 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12146307.fastq.gz | Fastqsanger.gz | |||
| SRR12146308.fastq.gz | Fastqsanger.gz | |||
| SRR12146309.fastq.gz | Fastqsanger.gz | |||
| SRR12146310.fastq.gz | Fastqsanger.gz | |||
| SRR12146311.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:Single nucleus RNA-Seq (snRNA-Seq) is used as an alternative to single cell RNA-Seq, as it allows transcriptomic profiling of frozen tissue. However, it is unclear whether snRNA-Seq is able to detect cellular state in human tissue. Indeed, snRNA-Seq analyses of human brain samples have failed to detect a consistent microglial activation signature in Alzheimer’s Disease. Our comparison of microglia from single cells and single nuclei of four human subjects revealed that, while the majority of genes showed similar relative abundances in cells and nuclei, a small population of genes (~1%) was depleted in nuclei compared to whole cells. This population was enriched for genes previously implicated in microglial activation, including APOE, CST3, SPP1, and CD74, comprising 18% of previously-identified microglial disease-associated genes. Given the low sensitivity of snRNA-Seq to detect many activation genes, we conclude that snRNA-Seq is not suited to detecting cellular activation in microglia in human disease.
2020-09-29 | GSE153807 | GEO
Project description:Single-nucleus RNA sequencing (snRNA-seq) is used as an alternative to single-cell RNA-seq, as it allows transcriptomic profiling of frozen tissue. However, it is unclear whether snRNA-seq is able to detect cellular state in human tissue. Indeed, snRNA-seq analyses of human brain samples have failed to detect a consistent microglial activation signature in Alzheimer's disease. Our comparison of microglia from single cells and single nuclei of four human subjects reveals that, although most genes show similar relative abundances in cells and nuclei, a small population of genes (∼1%) is depleted in nuclei compared to whole cells. This population is enriched for genes previously implicated in microglial activation, including APOE, CST3, SPP1, and CD74, comprising 18% of previously identified microglial-disease-associated genes. Given the low sensitivity of snRNA-seq to detect many activation genes, we conclude that snRNA-seq is not suited for detecting cellular activation in microglia in human disease.
| S-EPMC7527779 | biostudies-literature
Project description:Major Histocompatibility Complex I (MHC-I) CNS cellular localization and function is still being determined after previously being thought to be absent from the brain. MHC-I expression has been reported to increase with brain aging in mouse, rat, and human whole tissue analyses. Neuronal MHC-I has been proposed to regulate developmental synapse elimination and tau pathology in Alzheimer’s disease (AD). Here we report that across newly generated and publicly available ribosomal profiling, cell sorting, and single-cell data, microglia were the primary source of classical and non-classical MHC-I in mice and humans. Translating Ribosome Affinity Purification (TRAP)-qPCR analysis of 3-6 and 18-22 month old (m.o.) mice revealed significant age-related microglial induction of MHC-I pathway genes B2m, H2-D1, H2-K1, H2-M3, H2-Q6, and Tap1 but not in astrocytes and neurons. Across a timecourse (12-23 m.o.), microglial MHC-I gradually increased until 21 m.o. and then accelerated. MHC-I protein was also enriched in microglia and increased with aging. Microglial expression, and absence in astrocytes and neurons, of MHC-I binding Leukocyte Immunoglobulin-like (Lilrs) and Paired immunoglobin-like type 2 (Pilrs) receptor families could enable cell-autonomous MHC-I signaling and increased with aging in mice and humans. Increased microglial MHC-I, Lilrs, and Pilrs were observed in AD mouse models and human AD data is evident across numerous mouse models, methods, and studies. MHC-I expression correlated with p16INK4A, suggesting an association with cellular senescence. Conserved induction of MHC-I, Lilrs, and Pilrs with aging and AD opens the possibility of cell-autonomous MHC-I signaling to regulate microglial reactivation with aging and neurodegeneration.
2023-07-05 | GSE231604 | GEO
Project description:Microglial MHC-I induction with aging and Alzheimer’s is conserved in mouse models and humans
| PRJNA966986 | ENA
Project description:There is a paucity of data to guide anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) with brain sensing. The clinical Medtronic Percept DBS device provides constrained brain sensing power within a frequency band (power-in-band [PIB]), recorded in 10-min averaged increments. Here, four patients with temporal lobe epilepsy were implanted with an investigational device providing full bandwidth chronic intracranial electroencephalogram (cEEG) from bilateral ANT and hippocampus (Hc). ANT PIB-based seizure detection was assessed. Detection parameters were cEEG PIB center frequency, bandwidth, and epoch duration. Performance was evaluated against epileptologist-confirmed Hc seizures, and assessed by area under the precision-recall curve (PR-AUC). Data included 99 days of cEEG, and 20, 278, 3, and 18 Hc seizures for Subjects 1-4. The best detector had 7-Hz center frequency, 5-Hz band width, and 10-s epoch duration (group PR-AUC = .90), with 75% sensitivity and .38 false alarms per day for Subject 1, and 100% and .0 for Subjects 3 and 4. Hc seizures in Subject 2 did not propagate to ANT. The relative change of ANT PIB was maximal ipsilateral to seizure onset for all detected seizures. Chronic ANT and Hc recordings provide direct guidance for ANT DBS with brain sensing.
| S-EPMC10122837 | biostudies-literature
Project description:Microglial cells are resident macrophages in the central nervous system (CNS) and play a pivotal role in the innate and adaptive immune responses against microbial infections. The immune functions of microglia are regulated by a milieu of cytokines including interferon (IFN)-gamma. We here performed a series of experiments to acertain the transcriptional profile of human fetal microglial cells at 1, 6, and 24 h after IFN-gamma treatment. Primary human microglial cells were either untreated or treated with 200u/ml IFN-gamma. Affymetrix U133A chips were utilized. Four different tissue samples (B18, O, W, and Y20) were analyzed at the three time points.
2007-08-03 | E-GEOD-1432 | biostudies-arrayexpress
Project description:Microglial dysfunction is a key pathological feature of Alzheimer´s disease (AD), but little is known about proteome-wide changes in microglia during the course of AD pathogenesis and their consequences for microglial function. Here, we performed an in-depth proteomic characterization of microglia in two AD mouse models, the overexpression APPPS1 and the knock-in AppNL-G-F (APP-KI) model. Proteome changes were followed from pre-deposition to early, middle and advanced stages of amyloid plaque pathology, revealing a large panel of Microglial Amyloid Response Proteins (MARPs) that reflect a heterogeneity of microglial alterations triggered by Adeposition. We demonstrate that the occurrence of MARPs coincided with the deposition of fibrillar A, recruitment of microglia to amyloid plaques and phagocytic dysfunction. While the proteomic and functional microglial changes were already markedly seen in 3 months old APPPS1 mice, they were delayed in the APP-KI model that generates substantially less fibrillar A. The identified microglial proteomic fingerprints of AD provide a valuable resource for functional studies of novel molecular targets and potential biomarkers for monitoring AD progression or therapeutic efficacy.
2020-06-09 | PXD016075 | Pride
Project description:This project describes the proteome of a microglial cell line generated by differentiation of human SC.
2023-03-10 | PXD024649 | Pride
Project description:Microglia are versatile regulators in brain development and disorders. Emerging evidence links miRNA-mediated regulation to microglial function; however, the exact underlying mechanism remains largely unknown. Here, we discover that miR-137, a neuropsychiatric disorders-associated miRNA, is abundant in the microglial nucleus and exhibits unexpected epigenetic functions in maintaining the global transcriptomic state, core properties, and functions of microglia. Mechanistically, microglial Mir137 deletion increases the accessibility of chromatin, which harbors binding motifs of microglial master transcription factor Pu.1. Our biochemical and bioinformatics analyses suggest that miR-137 can interact with Pu.1, thus influencing Pu.1-mediated gene expression. Importantly, we find that increased Pu.1 binding upregulates the target gene Jdp2, and Jdp2 knockdown markedly suppresses the impaired cellular phenotypes in Mir137 knockout microglia. Collectively, our study provides evidence supporting a notion that miR-137 acts as an epigenetic regulator, and this microglia-specific function is essential to maintain normal adult brain function.
2024-02-22 | GSE222665 | GEO
Project description:Microglia are versatile regulators in brain development and disorders. Emerging evidence links miRNA-mediated regulation to microglial function; however, the exact underlying mechanism remains largely unknown. Here, we discover that miR-137, a neuropsychiatric disorders-associated miRNA, is abundant in the microglial nucleus and exhibits unexpected epigenetic functions in maintaining the global transcriptomic state, core properties, and functions of microglia. Mechanistically, microglial Mir137 deletion increases the accessibility of chromatin, which harbors binding motifs of microglial master transcription factor Pu.1. Our biochemical and bioinformatics analyses suggest that miR-137 can interact with Pu.1, thus influencing Pu.1-mediated gene expression. Importantly, we find that increased Pu.1 binding upregulates the target gene Jdp2, and Jdp2 knockdown markedly suppresses the impaired cellular phenotypes in Mir137 knockout microglia. Collectively, our study provides evidence supporting a notion that miR-137 acts as an epigenetic regulator, and this microglia-specific function is essential to maintain normal adult brain function.
2024-02-22 | GSE222663 | GEO