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Deep single-cell RNAseq of Gpnmb+Clec7a+ microglia from postnatal day 7 cerebellum

ABSTRACT: We generated single-cell RNAseq profiles of 143 microglia, sorted in the gate CD45lowCD11+Gpnmb+Clec7a+, from postnatal day 7 cerebellum to validate the newly identified “proliferative region-associated microglia (PAM)” (Gpnmb and Clec7a are PAM surface markers). Single cells were FACS index sorted followed by Smart-seq2 library preparation and Illumina Nextseq (sequence depth > 1 million per cell). These cells showed characteristic PAM gene expression and clustered together with other PAM cells sequenced in the same study.

ORGANISM(S): Mus musculus

PROVIDER: GSE123024 | GEO | 2018/12/31

REPOSITORIES: GEO

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Deep single-cell RNAseq of postnatal day 7 microglia from wild type and Trem2 knockout brains

Project description:We generated single-cell RNAseq profiles of 369 microglia (183 from wild type and 186 from Trem2 knock-out), sorted in the gate CD45lowCD11+ or CD45lowCD11+Gpnmb+Clec7a+ (PAM enrichment), to compare gene expression of wild type vs. Trem2 knock-out microglia on the postnatal day 7. Single cells were FACS index sorted from the whole brain followed by Smart-seq2 library preparation and Illumina Nextseq (sequence depth > 1 million per cell). A total of 334 cells passed quality control for data analysis. Microglia in the Trem2 knock-out contained a similar PAM population with characteristic gene expression, suggesting that the presence of early postnatal PAM do not depend on TREM2.

2018-12-31 | GSE123022 | GEO

Deep single-cell RNAseq of Gpnmb+Clec7a+ microglia from postnatal day 7 cerebellum

Project description:Deep single-cell RNAseq of Gpnmb+Clec7a+ microglia from postnatal day 7 cerebellum

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Microarray gene expression profiling of a fibrosarcoma GPNMB-induced cell line MCA-1-GPNMB at basal condition and in the form of spheroids

Project description:The expression of the soluble protein GPNMB (glycoprotein non-metastatic melanoma protein B) induces an aggressive behavior of tumor cells by promoting proliferation and distant spread. The main molecular feature is the over expression of interleukin Il-33. The gene profile of MCA-1-GPNMB and MCA-1-GPNMB-spheroid cell line was assessed against MCA-1-Mock.

2020-07-30 | E-MTAB-8082 | biostudies-arrayexpress

GPNMB confers risk for Parkinson’s disease through interaction with alpha-synuclein

Project description:Many risk loci for Parkinson’s disease (PD) have been identified by genome-wide association studies (GWAS), but target genes and mechanisms remain largely unknown. We linked the GWAS-derived chromosome 7 locus (sentinel SNP rs199347) to GPNMB, through colocalization analyses of expression quantitative trait locus (eQTL) and PD risk signals, confirmed by allele-specific expression studies in human brain. In cells, Glycoprotein Nonmetastatic Melanoma Protein B protein (GPNMB) co-immunoprecipitated and co-localized with alpha-synuclein (aSyn). In induced pluripotent stem cell-derived neurons, loss of GPNMB resulted in loss of ability to internalize aSyn fibrils and develop aSyn pathology. In 781 PD and 59 control biosamples, GPNMB was elevated in PD plasma, associating with disease severity. Thus, GPNMB represents a PD risk gene, with potential for biomarker development and therapeutic targeting.

2022-06-17 | GSE206327 | GEO

Deep single-cell RNAseq of microglia and brain myeloid cells from various brain regions and developmental stages

Project description:We generated single-cell RNAseq profiles of microglia and brain myeloid cells (1922 total; 1816 cells passed quality control) from different developmental stages (E14.5, P7 and P60) to study their heterogeneity. Cells were isolated from either the whole developing brain (for the E14.5 stage) or six separate regions (for P7 and P60 stages): Cortex (CTX), Cerebellum (CB), Hippocampus (HIP), Striatum (STR), Olfactory bulb (OB), Choroid plexus (CP). Single cells were FACS index sorted followed by Smart-seq2 library preparation and Illumina Nextseq (sequence depth > 1 million per cell). All 1816 cells were grouped into 15 clusters using Seurat package (Macosko, Basu, Satija et al. Cell. 2015), and manually annotated based on gene expression signatures and meta data. We found that the majority of adult microglia expressing homeostatic genes are remarkably similar in transcriptomes, regardless of brain region. By contrast, postnatal microglia represent a more heterogeneous population. We discovered a proliferative region-associated microglia (PAM) subset, mainly found in developing white matter, that share a characteristic gene signature with degenerative disease-associated microglia (DAM). Such PAM have amoeboid morphology, are metabolically active, and phagocytose newly formed oligodendrocytes. This scRNA-seq atlas will be a valuable resource for dissecting innate immune functions in health and disease.

2018-12-31 | GSE123025 | GEO

Elevated gpNMB in type 1 Gaucher disease patients

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2016-09-27 | PXD001598 | Pride

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Project description:Metabolism in mammals is regulated by the complex interplay among different organs. Fatty acid synthesis is increased in white adipose tissue (WAT) when it is inhibited in liver. Here we identify glycoprotein nonmetastatic melanoma protein B (Gpnmb) as one liver-WAT cross-talk factor in lipogenesis. Hepatic SREBP pathway inhibition leads to increased transcription of the Gpnmb and promotes the processing of the membrane protein to a secreted form. Gpnmb stimulates lipogenesis in WAT and exacerbates diet-induced obesity and insulin resistance. In humans, Gpnmb is tightly associated with body mass index and is a strong risk factor for obesity. Gpnmb inhibition by a neutralizing antibody or liver specific knockdown improves metabolic parameters including weight gain reduction and increased insulin sensitivity, likely by promoting the beiging of WAT. These results suggest that Gpnmb is a liver-secreted factor regulating lipogenesis in WAT, and that Gpnmb inhibition may provide a therapeutic strategy for obesity and diabetes. Hepatic SREBP pathway inhibition, such as liver-specific ablation of Scap (L-Scap-/-), decreases fatty acid synthesis in liver. Meanwhile, the fatty acid synthesis in white adipose tissue of L-Scap-/- is compensatorily increased. The microarray analysis using the liver RNAs of L-Scap-/- and wild type (WT) mice is performed to identify the up-regulated genes encoding secreted factors in L-Scap-/-.

2019-04-04 | GSE129283 | GEO

gene expression of aorta of ApoE KO mice after Gpnmb vaccine treatment

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2021-10-22 | GSE155596 | GEO

Role of Gpnmb in response to virally expressed mutant SNCA

Project description:Effect of Gpnmb knockout on development of differential expression in AAV-aSyn model was studied. The "samid" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech's ExpressionPlot database is PRJ0036339

2021-06-18 | GSE163559 | GEO

Role of Gpnmb in response to PFF-induced spreading alpha-synucleinopathy

Project description:Effect of Gpnmb knockout on development of differential expression in PFF-aSyn model was studied. The "sample_id" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech's ExpressionPlot database is PRJ0036142

2021-06-18 | GSE163727 | GEO

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