Breast Milk-Associated Oxysterol Reverses Neonatal Brain Injury Through Gli2-Dependent Oligodendrogenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA497608 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We identified an emerging oligodendrocyte committed subpopulation based on their gene expression that included Pdgfra, Cspg4 also known as Ng2, Olig1, Olig2.
2018-10-20 | GSE121540 | GEO
Project description:White matter injuries (WMIs) are the leading cause of neurologic impairment in infants born premature. There are no treatment options available. The most common forms of WMIs in infants occur prior to the onset of normal myelination, making its pathophysiology distinctive, thus requiring a tailored approach to treatment. Neonates present a unique opportunity to repair WMIs due to a transient abundance of neural stem/progenitor cells (NSPCs) present in the germinal matrix with oligodendrogenic potential. We identified an endogenous oxysterol, 20-αHydroxycholesterol (20HC), in human maternal breast milk that induces oligodendrogenesis through a sonic hedgehog (shh), Gli-dependent mechanism. Following WMI in neonatal mice, injection of 20HC induced subventricular zone-derived oligodendrogenesis and improved myelination in the periventricular white matter, resulting in improved motor outcomes. Targeting the oligodendrogenic potential of postnatal NSPCs in neonates with WMIs may be further developed into a novel approach to mitigate this devastating complication of preterm birth.
| S-EPMC10625465 | biostudies-literature
Project description:We used genome-wide microarray comparative genomic hybridization to investigate the response of control HT1080 cells and HT1080 cells infected with a lentivirus expressing eGFP, GLI2-eGFP or CCND1-RFP to challenge with methotrexate to address the question if GLI2 overexpression induces genomic instability. Keywords: aCGH Array CGH experiments of cell line genomic DNA as test samples and normal human genomic DNA as reference sample.
2009-01-05 | E-GEOD-10132 | biostudies-arrayexpress
Project description:It has been reported that GLI2 promotes proliferation, migration, and invasion of mesenchymal stem cell and osteosarcoma cells. To examine the molecular mechanisms of GLI2-mediated osteosarcoma metastasis, we performed a microarray analysis. The gene encoding ribosomal protein S3 (RPS3) was identified as a target of GLI2. Real-time PCR revealed that RPS3 was upregulated in osteosarcoma cell lines compared with normal osteoblast cells. Knockdown of GLI2 decreased RPS3 expression, whereas forced expression of a constitutively active form of GLI2 upregulated the expression of RPS3. RPS3 knockdown by siRNA decreased the migration and invasion of osteosarcoma cells. Although forced expression of constitutively active GLI2 increased the migration of human mesenchymal stem cells, knockdown of RPS3 reduced the up-regulated migration. In contrast, forced expression of RPS3 increased migration and invasion of osteosarcoma cells. Moreover, reduction of migration by GLI2 knockdown was rescued by forced expression of RPS3. Immunohistochemical analysis showed that RPS3 expression was increased in primary osteosarcoma lesions with lung metastases compared with those without. These findings indicate that GLI2–RPS3 signaling may be a marker of invasive osteosarcoma and a therapeutic target for patients with osteosarcoma.
2012-12-14 | GSE42903 | GEO
Project description:We used genome-wide microarray comparative genomic hybridization to investigate the response of control HT1080 cells and HT1080 cells infected with a lentivirus expressing eGFP, GLI2-eGFP or CCND1-RFP to challenge with methotrexate to address the question if GLI2 overexpression induces genomic instability. Keywords: aCGH
2009-01-06 | GSE10132 | GEO
Project description:Chromatin immunoprecipitation with anti-GLI2 antibody was conducted in human pulomonary microvascular endothelial cells (HPMECs) to determine GLI2 binding sites upstream of FOXF1. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides and their functions remain enigmatic. We demonstrate that deletions of lncRNA genes cause a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV), with parent of origin effects. We identify non-coding overlapping deletions 250 kb upstream to FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete a fetal lung-specific EST, part of an lncRNA. These deletions define distant cis-regulatory region that harbors a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter, consistent with the absence of the fetal lung-transcribed lncRNA perturbing FOXF1 regulation. LncRNA-mediated chromatin interactions may be responsible for position effect phenomenon and potentially cause many disorders of human development. ChIP-chip HPMECs transfected to overxpress GLI2; 2 biological replicates
2012-07-10 | E-GEOD-39255 | biostudies-arrayexpress
Project description:THP-1 monocytes were differentiated, via PMA treatment, to macrophages. THP-1 macrophages were then treated with a mixed-oxysterol treatment (7-ketocholesterol and 7beta-hydroxycholesterol) for 24 hours. The mixed-oxysterol treatment was mixed to a ratio that represents the cytotoxic oxysterol content of human atherosclerotic plaque. Control and treated macrophages were analysed using both 2-DE with peptide mass-fingerprinting and tandem-mass spectrometry.
2017-03-15 | PXD004304 | Pride
Project description:The capacity of stem cells to maintain and regenerate organs is critically dependent on the niche, a complex signaling microenvironment that sustains and regulates stem cell activity. Niche function in the mammary gland must integrate local homeostatic activities with hormonally regulated events, such as pregnancy or the onset of puberty. In the human disorder CPHD (combined pituitary hormone deficiency) breast growth defects at puberty are associated with mutations disrupting the transcription factor, GLI2. Here we find that Gli2 functions in mouse mammary stromal cells to shape a niche signaling program that sustains mammary epithelial stem cells. Ablation of Gli2 in stromal cells thus leads to a disorganized mammary gland, associated with collapse of the niche signaling environment, with a five-fold decrease in functional mammary stem cell activity, and with attenuated response to the mammatrophic hormones estrogen and growth hormone. Consistent with a niche defect, aspects of Gli2-deficient mammary gland architecture can be rescued by local supplementation with IGF and WNT protein signals. Our findings thus identify GLI2 as a critical coordinator of local and hormonal influences on the niche signaling program, and suggest that mammary pathogenesis in CPHD patients results from dysfunction of the mammary epithelial stem cell niche. We used microarrays to identify gene expression signatures associated with stromal Gli2 expression
2015-03-13 | GSE66820 | GEO
Project description:Metabolism of anticancer drugs markedly affects their antitumor effects. The major goal of our study was to investigate associations of gene expression of enzymes metabolizing taxanes and/or anthracyclines with therapy response and survival of breast carcinoma patients The present study investigated transcript levels of key modulators of oxysterol signaling pathway, including oxysterol receptors, metabolic enzymes and transporters in the group of hormone-receptor positive breast carcinoma patients to evaluated potential clinical significance of these genes.
2017-04-06 | GSE85206 | GEO
Project description:Excessive Hedgehog signaling in chondrocytes is sufficient to cause formation of enchondroma-like lesions in mice which can progress to chondrosarcoma. To elucidate potential mechanisms through which activation of Hedgehog signaling contributes to cartilage tumor formation, we used chromatin immunoprecipitation and next generation sequencing to identify Gli1 and Gli2 target genes in primary human chondrosarcoma. In silico analyses were conducted to identify and characterize Gli1 and Gli2 binding regions, including de novo motif analysis, co-localization with additional transcription factors, distance to transcriptional start site, conservation between human and mouse, and supervised and unsupervised analyses of biological pathways and processes. Our results profile putative unique and overlapping target genes of Gli1 and Gli2 in chondrosarcoma.
2019-12-12 | GSE100936 | GEO