Neural Epidermal Growth Factor-Like Like Protein 2 (NELL2) is Expressed in Human Oligodendroglial Cell types
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PROVIDER: PRJNA787887 | ENA |
REPOSITORIES: ENA
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Project description:NELL2 is a cytoplasmic and secreted glycosylated protein with six epidermal growth factor-like domains. In animal models, Nell2 is predominantly expressed in neural tissues where it regulates neuronal differentiation, polarization, and axon guidance, but little is known about the role of NELL2 in human brain development. In this study, we show that rostral neural stem cells (rNSC) derived from human iPSC exhibit particularly strong NELL2 expression, and that NELL2 protein is enriched at the apical side of neural rosettes in hiPSC derived brain organoids. Following differentiation of human rostral NSC into neurons, NELL2 remains robustly expressed but changes its subcellular localization from >20 small cytoplasmic foci in NSC to 1-5 large peri-nuclear puncta per neuron. Unexpectedly, we discovered that in human brain organoids NELL2 is readily detectable in oligodendroglia and that the number of NELL2 puncta increases as oligodendrocytes mature. Artificial intelligence-based machine learning further predicts a strong association of NELL2 with multiple human white matter diseases, suggesting that NELL2 may possess yet unexplored roles in regulating oligodendrogenesis and/or myelination during human cortical development and maturation.
2021-12-13 | GSE190633 | GEO
Project description:Neural EGFL-like 2 (NELL2) is a secreted protein known for its regulatory functions in the nervous and reproductive systems, yet its role in bone biology remains unexplored. In this study, we observed that the NELL2 levels were diminished in the serum of osteoporosis patients, as well as in the bone of aged and ovariectomized (OVX) mice. In vitro loss-of-function and gain-of-function studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from mesenchymal progenitor cells. In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in a low bone turnover phenotype characterized by decreased cancellous bone mass in mice. Mechanistically, we identified Fibronectin 1 (Fn1) as a potential receptor for NELL2. Specifically, NELL2 interacted with the FNI-type domain located at the C-terminus of Fn1. Moreover, we found that NELL2 activated the focal adhesion kinase (FAK)/AKT signaling pathway through Fn1/integrin β1 (ITGB1), leading to the promotion of osteogenesis and the inhibition of adipogenesis. Notably, administration of NELL2-AAV was found to ameliorate bone loss in OVX mice. These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis, suggesting its potential as a therapeutic target for managing osteoporosis.
2025-04-11 | GSE266198 | GEO
Project description:Purpose: The goal of this study is to detect differentially expressed genes, between Wild type (WT) and Nell2-/- (Nell2-KO) caput epididymis by RNA sequencing Methods: Caput epidiymal mRNA profiles of 14-week-old wild-type (WT) and NEL-like 2 knockout (Nell2-KO) mice were generated by deep sequencing, in quadplicate, using Illumina GAIIx. Results: RNA-seq data identified differentially expressed transcripts; 26 genes showed differential transcript expression between the WT and Nell2-KO caput epididymis, with WT RPKM ≥100, a fold change ≤0.1, and t-test p value <0.05. Altered expression of 26 genes identified. Conclusions: Our results show that the expression of many genes were downregulated in Nell2-KO caput epididymis compared with WT one.
2020-06-05 | GSE133920 | GEO
Project description:Multiple sclerosis (MS) is the most frequent demyelinating disease and despite significant advances in the immunotherapy, disease progression still cannot be prevented. Promotion of remyelination, an endogenous repair process, represents a promising new treatment approach. However, spontaneous remyelination frequently fails in MS lesions due to an impaired differentiation of progenitor cells into mature, myelinating oligodendrocytes. Intrinsic oligodendroglial and extrinsic inflammatory factors may contribute to this differentiation block. Therefore, we compared induced pluripotent stem cell (iPSC)-derived oligodendrocytes (hiOL) from MS patients and healthy controls as well as their response to extrinsic factors. While functional capabilities or proteome compostion of both cell types were virtually indistinguishable, we discovered that Interferon-gamma (IFNγ) producing immune cells significantly impaired oligodendroglial differentiation and observed no differences in the functional capabilities or the proteome. In summary, these data indicate that the oligodendroglial differentiation block is not due to intrinsic oligodendroglial factors, but rather caused by the inflammatory environment present in MS lesions. These findings may contribute to the development of remyelination promoting strategies in MS.
2020-09-04 | PXD016043 | Pride
Project description:Neural EGFL-like 2 (NELL2) is a secreted protein known for its regulatory functions in the nervous and reproductive systems, yet its role in bone biology remains unexplored. In this study, we observed that the NELL2 levels were diminished in the serum of osteoporosis patients, as well as in the bone of aged and ovariectomized (OVX) mice. In vitro loss-of-function and gain-of-function studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from mesenchymal progenitor cells. In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in a low bone turnover phenotype characterized by decreased cancellous bone mass in mice. Mechanistically, we identified Fibronectin 1 (Fn1) as a potential receptor for NELL2. Specifically, NELL2 interacted with the FNI-type domain located at the C-terminus of Fn1. Moreover, we found that NELL2 activated the focal adhesion kinase (FAK)/AKT signaling pathway through Fn1/integrin β1 (ITGB1), leading to the promotion of osteogenesis and the inhibition of adipogenesis. Notably, administration of NELL2-AAV was found to ameliorate bone loss in OVX mice. These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis, suggesting its potential as a therapeutic target for managing osteoporosis.
2025-04-11 | GSE265936 | GEO
Project description:Purpose: The purpose of this study is to characterize genes whose expressions in the initial segment (IS)-caput epididymis were affected by unilateral orchidectomy (UOD), bilateral orchidectomy (BOD), and Nell2 gene ablation. Methods: The unilateral or bilateral orchidectomy of WT mice was performed from 8 weeks old and continued for 4 weeks until tissue sampling at 12 weeks old. Contralateral epididymis was used as a control for UOD. Sham operation was also done as a control for BOD. Nell2-/- mice and their control WT mice were used wthen they were 14-week-old. IS-caput epididymal mRNA profiles were generated by deep sequencing, in triplicate, using Illumina NovaSeq6000. Results: RNA-seq data identified differentially expressed transcripts. Conclusions: Our results show that the expression of many genes was affected by UOD, BOD, and Nell2 ablation.
2023-11-19 | GSE247764 | GEO
Project description:Oligodendroglial cells are responsible for the generation of myelin sheaths in the central nervous system and thereby render rapid saltatory conduction possible. During development, oligodendroglial cells express the three paralogous transcription factors Sox8, Sox9 and Sox10. In mature oligodendrocytes Sox8 and Sox10 expression persists. Whereas Sox9 and Sox10 fulfill important regulatory roles in these cells, Sox8 has only a limited impact on oligodendroglial development and myelination. By replacing Sox10 with Sox8 or Sox9 in the oligodendroglial Oln93 cell line and by comparing expression profiles, we show that Sox8 regulates the same processes as Sox10 and Sox9, but has a substantially lower transcriptional activity under standard culture conditions.
2025-01-02 | GSE280389 | GEO
Project description:Coexpression of alpha-synuclein and p25alpha in an oligodendroglial cell line elicites a degenerative response that relies on aggregation and phosphorylation of alpha-synuclein at Ser129 We used microarray analysis to detail the changes in gene expression caused by alpha-synuclein aggregation followed by cellular degeneration Alpha-synuclein was coexpressed with p25alpha in an oligodendroglial cell line and mRNA was isolated at 8, 12, and 16 hrs after transfection. Gene expression was analyzed by two identical microarray set-ups
2013-10-28 | E-GEOD-51781 | biostudies-arrayexpress
Project description:Coexpression of alpha-synuclein and p25alpha in an oligodendroglial cell line elicites a degenerative response that relies on aggregation and phosphorylation of alpha-synuclein at Ser129 We used microarray analysis to detail the changes in gene expression caused by alpha-synuclein aggregation followed by cellular degeneration
2013-10-28 | GSE51781 | GEO
Project description:Gene expression profiling of epidermal cell types in C. elegans using Targeted DamID
| PRJNA691926 | ENA