Effect of Fn1 knockdown or NELL2 overexpression on gene expression in stromal ST2 cells
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ABSTRACT:
PROVIDER: PRJNA1104997 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28818806_1.fastq.gz | Fastqsanger.gz | |||
| SRR28818806_2.fastq.gz | Fastqsanger.gz | |||
| SRR28818807_1.fastq.gz | Fastqsanger.gz | |||
| SRR28818807_2.fastq.gz | Fastqsanger.gz | |||
| SRR28818808_1.fastq.gz | Fastqsanger.gz |
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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: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:As a key protein in the tumor microenvironment, FN1 has been proven to promote cancer in a variety of cancer species. However, in our previous study on gastric cancer, it was found that FN1 protein expression in patient tissues was not significantly correlated with prognosis, and clinical data analysis was only correlated with T stage of gastric cancer. Analysis of the relationship between FN1 mRNA expression level and prognosis by TCGA-STAD database revealed that high FN1 mRNA expression was significantly correlated with poor prognosis. Moreover, many miRNA binding sites were found on FN1 3' UTR by database prediction, so we speculated that FN1 played different functions at mRNA and protein levels, and FN1 3' UTR might function as ceRNA. At present, FN1 3' UTR overexpression has been proved to significantly promote the invasion and metastasis of gastric cancer in vivo and in vitro, and its effect is stronger than FN1 protein. Therefore, in this study, miRNA sequencing, which was used to find those miRNAs bound to FN1 3’UTR, was carried out to further explore its cancer-promoting mechanism.
2022-02-27 | GSE197423 | GEO
Project description:As a key protein in the tumor microenvironment, FN1 has been proven to promote cancer in a variety of cancer species. However, in our previous study on gastric cancer, it was found that FN1 protein expression in patient tissues was not significantly correlated with prognosis, and clinical data analysis was only correlated with T stage of gastric cancer. Analysis of the relationship between FN1 mRNA expression level and prognosis by TCGA-STAD database revealed that high FN1 mRNA expression was significantly correlated with poor prognosis. Moreover, many miRNA binding sites were found on FN1 3' UTR by database prediction, so we speculated that FN1 played different functions at mRNA and protein levels, and FN1 3' UTR might function as ceRNA. At present, FN1 3' UTR overexpression has been proved to significantly promote the invasion and metastasis of gastric cancer in vivo and in vitro, and its effect is stronger than FN1 protein. Therefore, in this study, transcriptome sequencing of FN1 3' UTR after overexpression was carried out to further explore its cancer-promoting mechanism.
2022-02-27 | GSE197422 | GEO
Project description:In diabetics, methylglyoxal (MG), a glucose-derived metabolite, plays a noxious role by inducing oxidative stress, which causes and exacerbates a series of complications. With the use of microarray analysis, we comprehensively screened the gene expression profiles of ST2 cells, derived from a multipotent bone marrow stromal cell line, in the presence or absence of oxidative stress induced by100 M-NM-<M methylglyoxal (MG) treatment to charactrize genes related to diabetic complications. Mouse bone marrow stromal cell-line ST2 (RIKEN, Tsukuba, Japan) was cultured in M-NM-1-MEM (Sigma, St. Louis, MO) supplemented with 10% FBS (Sigma), 100 M-NM-<g/ ml penicillin/ streptomycin (ICN Biomedicals, Inc., Aurora, OH) and 100 M-NM-<M methylglyoxal (MG), and maintained at 37M-BM-0C in a humidified atmosphere with 5% CO2. Total RNA was isolated from ST2 cells treated with or without 100 M-NM-<M methylglyoxal (MG) or 1 M-NM-<M of 5-aza-2M-bM-^@M-^Y-deoxycytidine (5-aza-dC) by standard methods with the use of an RNeasy Protect Mini kit (Qiagen KK, Tokyo, Japan) according to the manufacturerM-bM-^@M-^Ys instructions. Cy3, Cy5 differential expression asasy by Mouse 32K Filgen array
2013-11-19 | E-GEOD-52475 | biostudies-arrayexpress
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: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:Colorectal cancer (CRC) was induced in Foxp3/eGFP reporter mice by the azoxymethane/dextran sulphate sodium salt (AOM/DSS) protocol. Mice were injected i.p. with the procarcinogen AOM (12.5 mg/kg of body weight). After 1 week, mice received drinking water supplemented with 2.5% DSS for 5 to 7 days, followed by 2 weeks of regular water. The DSS administration was repeated twice with 2% DSS. Mice were sacrificed at week 11 and lamina propia lymphocytes (LPLs) from the colon were isolated. CD4+FOXP3+ (eGFP+) ST2+ or ST2- Tregs were separated from colonic LPLs of CRC induced mice using a FACSAria II cell sorter. Microarray analysis was performed to analyze if ST2+ FOXP3+ Tregs from the colon of CRC mice present a distinct transcription pattern compared to ST2- FOXP3+ Tregs. By this, the role of ST2 for Treg function during intestinal tumorigenesis should be characterized.
2019-05-31 | E-MTAB-6842 | biostudies-arrayexpress
Project description:Foxp3+ regulatory T cells (Tregs) are critical mediators of peripheral tolerance and immune homeostasis. Tregs that express the IL-33 receptor ST2 are enriched in peripheral nonlymphoid tissues and can exert a variety of tissue-specific functions from metabolic regulation within adipose tissue to skeletal muscle repair. However, the relationship between ST2+ and ST2- Tregs within and across different tissues remains unclear. To compare murine ST2- and ST2+ Tregs within and across tissues, we performed RNA sequencing (RNAseq) of ST2-CD44hi and ST2+CD44hi Tregs from blood, spleen, lungs, visceral adipose tissue (VAT), colon, and skin. RNAseq was also performed on ST2- CD44lo CD62L+ Tregs from the spleen and lungs. We found that the tissue microenvironment was the major factor shaping the transcriptome of Tregs across tissues. Across the tissues studied, Treg transcriptomes displayed an ordered hierarchy that may represent graded levels of activation or differentiation across tissues. We also identified a core signature that distinguished ST2+ Tregs from ST2- Tregs across tissues and a large number of differentially expressed genes between ST2- and ST2+ Tregs within individual tissues that could support the tissue-specific adaptation and function of ST2+ Tregs. In summary, our work highlights the unique, tissue-specific phenotype of ST2+ Tregs and reveals a core ST2+ Treg transcriptional signature shared across tissues.
2022-07-24 | GSE182322 | GEO
Project description:Maf1, a key repressor of RNA polymerase III-mediated transcription, has been shown to promote mesoderm formation in vitro. Here, we show, for the first time, that Maf1 plays a critical role in the regulation of osteoblast differentiation. We also found that, in contrast to MAF1 overexpression, other perturbations that repress RNA pol III transcription, including Brf1 knockdown and the chemical inhibition of RNA pol III by ML-60218, inhibited osteoblast differentiation. RNA-seq was used to determine the basis for these opposing actions on osteoblast differentiation. RNA polymerase III-dependent transcription was manipulated in ST2 stromal cells by Brf1 or Maf1 knockdown, ML-60218 treatment and MAF1 overexpression. The ST2 cells were then tested for their capacity to differentiate into osteoblasts. RNA-seq was performed on day 0, before differentiation and day 4 after differentiation medium was added. The modalities used to perturb RNA pol III transcription resulted in distinct changes gene expression, indicating that this transcription process is highly sensitive and triggers diverse gene expression programs and phenotypic outcomes. Specifically, Maf1 induced genes in ST2 cells known to promote osteoblast differentiation. Furthermore, genes that are induced during osteoblast differentiation displayed codon bias.
2022-05-20 | GSE203308 | GEO