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SRP099137
Homo sapiens
24 Downloadable Samples
Illumina HiSeq 2000
Description
Purpose: Identification of relevant genetic pathways that are altered with aging knowing that the precursors for bone-forming osteoblasts reside in the mesenchymal cell population of bone marrow. Method: harvested and characterized, without in vitro culture, mesenchymal cells form human bone marrow capable of osteogenic differentiation Results: Identification of differentially regulated genes with aging in a highly enriched human bone marrow mesenchymal cell population. Conclusions: we have for the first time identified age-related differential gene expression and DNA methylation patterns in a highly enriched human bone marrow mesenchymal cell populationprofiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions. Overall design: Examination of gene expression and DNA methylation patterns from a highly enriched bone marrow mesenchymal cell population from young (mean age, 28.7 years) versus old (mean age, 73.3 years) women
Publication Title
Global transcriptional profiling using RNA sequencing and DNA methylation patterns in highly enriched mesenchymal cells from young versus elderly women.
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Specimen part, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
The p90 ribosomal S6 kinase (RSK) family, a downstream target of Ras/extracellular signal-regulated kinase (ERK) signaling, can mediate cross-talk with the mammalian target of rapamycin complex 1 (mTORC1) pathway. As RSK connects two oncogenic pathways in gliomas, we investigated the protein levels of the RSK isoforms RSK1-4 in non-tumoral brain (NB) and grade I-IV gliomas. RSK4 expression was not detected in any brain tissues, whereas RSK3 expression was very low, with GBMs demonstrating the lowest RSK3 protein levels. When compared to NB or low-grade gliomas (LGG), a group of glioblastomas (RSK1hi) that excluded long-survivor cases expressed higher levels of RSK1. No difference was observed in RSK2 median-expression levels among NB and gliomas; however, high levels of RSK2 in glioblastomas (GBM) were associated with worse survival. RSK1hi and, to a lesser extent, RSK2hi GBMs, showed higher levels of phosphorylated RSK, which indicates RSK activation. Transcriptome analysis indicated that most RSK1hi GBMs belonged to the mesenchymal subtype, and RSK1 expression strongly correlated with gene expression signature of immune infiltrates, in particular of activated-natural killer cells and M2 macrophages. In an independent cohort, we confirmed that RSK1hi GBMs exclude long-survivors, and RSK1 expression was associated with high protein levels of the mesenchymal subtype marker LAPTM5, as well as with high expression of CD68, which indicated the presence of infiltrating immune cells. An RSK1 signature was obtained based on differentially expressed mRNAs and validated in public glioma datasets. Enrichment of RSK1 signature followed glioma progression, recapitulating RSK1 protein expression, and was associated with worse survival not only in GBM but also in LGG. In conclusion, both RSK1 and RSK2 associate with glioma malignity, but displaying isoform-specific peculiarities. The progression-dependent expression and association with immune infiltration, suggests RSK1 as a potential progression marker and therapeutic target for gliomas.
Publication Title
Aberrant expression of RSK1 characterizes high-grade gliomas with immune infiltration.
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