Project description:Global gene expressions of human bone-derived 11Lin-CD45-CD271+SSEA-4+ mesenchymal stem/stromal cells from young and elderly patients were analyzed. Results provide an insight into the molecular mechanisms of aging and cellular senescence.
Project description:This SuperSeries is composed of the following subset Series: GSE35955: Effects of aging on Human Mesenchymal Stem Cells GSE35956: Effects of Primary Osteoporosis and Advanced Age on Human Mesenchymal Stem Cells GSE35957: Effects of Cellular Senescence on Human Mesenchymal Stem Cells GSE35958: Effects of Primary Osteoporosis on Human Mesenchymal Stem Cells Refer to individual Series
Project description:Understanding how cells respond to the mechanics of their environment, and what affect senescence may have on this response, is important to gain a better understanding of mechanobiology, both in health and ageing-associated pathology. This experiment assessed the mRNA levels in early and late passage donor-matched human mesenchymal stem cells (MSCs) cultured for four days on soft (2 kPa) or stiff (25 kPa) collagen-I coated polyacrylamide (PA) gels. A minimum of three donors were analysed under each condition. Protein coding RNAs were sequenced with Illumina HiSeq technology. In a parallel experiment, protein was quantified by mass spectrometry proteomics.
Project description:Adult cardiac progenitor/stem cells (CPC/CSC) are multipotent resident populations involved in cardiac homeostasis and heart repair. Assisted by complementary RNAseq analysis, we defined the proteome fraction associable to specific CPC functions by comparison with human mesenchymal stem cells (MSC), the reference population for cell therapy. Label-free proteomics analysis identified 526 proteins expressed differentially in CPC. Quantitative iTRAQ analysis confirmed differential expression of a substantial proportion of these proteins expressed specifically in CPC relative to MSC. Systems biology analysis defined a clear overrepresentation of several categories related to enhanced angiogenic potential. The CPC plasma membrane compartment is comprised by 1595 proteins including a minimal signature of 167 proteins expressed preferentially in CPC. Of these core CPC functions, we selected a panel of 15 predicted cell surface markers and validated high differential expression of CDH5, CD200 and F11R in CPC.
Project description:Glioblastoma (GBM) is the most prevalent and aggressive malignant primary brain tumor. GBM proximal to the lateral ventricles (LVs) is more aggressive, potentially due to subventricular zone (SVZ) contact. Despite this, crosstalk between GBM and neural stem/progenitor cells (NSC/NPCs) is not well understood. Using cell-specific proteomics, we show that LV-proximal GBM prevents neuronal maturation of NSCs through induction of senescence. Additionally, GBM brain tumor initiating cells (BTICs) increase expression of CTSB upon interaction with NPCs. Lentiviral knockdown and recombinant protein experiments reveal both cell-intrinsic and soluble CTSB promote malignancy-associated phenotypes in BTICs. Soluble CTSB stalls neuronal maturation in NPCs while promoting senescence, providing a link between LV-tumor proximity and neurogenesis disruption. Finally, we show LV-proximal CTSB upregulation in patients, showing the relevance of this crosstalk in human GBM biology. These results demonstrate the value of proteomic analysis in tumor microenvironment research and provide direction for new therapeutic strategies in GBM.