Dataset Information

The protein profiles of neural stem cells

ABSTRACT: Stemazole was reported to induce the survival of human neural stem cells in the absence of growth factors and to have therapeutic effects on neurodegenerative diseases. However, the molecular mechanisms of stemazole against apoptosis are ambiguous. In this study, tandem mass tag (TMT)-based proteomics was performed to obtain whole protein expression profiles of human neural stem cells in different groups, which was performed with or without stemazole and under extreme conditions. Bioinformatics analysis based on protein–protein interaction (PPI) network construction, gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis were adopted to explore crucial proteins and possible pharmaco-logical mechanisms. A total of 77 differentially expressed proteins were identified, comprising 38 upregulated proteins and 39 downregulated proteins. FN1(Fibronectin), Asparagine synthetase (ASNS), Phosphoserine aminotransferase (PSAT1), PKA C-alpha (PRKACA), Phospholipase C beta3 (PLCB

ORGANISM(S): Homo Sapiens

SUBMITTER: Mei Han

PROVIDER: PXD032898 | iProX | Sat Apr 02 00:00:00 BST 2022

REPOSITORIES: iProX

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Publications

A Quantitative Proteomic Approach Explores the Possible Mechanisms by Which the Small Molecule Stemazole Promotes the Survival of Human Neural Stem Cells.

Chen Mingzhu M Zhu Yizi Y Li Huajun H Zhang Yubo Y Han Mei M

Brain sciences 20220525 6

Neurodegenerative disorders have become a serious healthcare problem worldwide and there is no efficacious cure. However, regulating the fate of stem cells is an effective way to treat these neurological diseases. In previous work, stemazole was reported to maintain the survival of human neural stem cells in the absence of growth factors and to have therapeutic effects on neurodegenerative diseases. However, although it is a promising small molecule, the molecular mechanisms against apoptosis ar ...[more]

PMID: 35741576

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Project description:Sivakumar2011_WntSignalingPathway The secreted protein Wnt activates the heptahelical receptor Frizzled on nieghboring cells. Activation of Frizzled causes the recruitment of additional membrane proteins which in turn result in 1) the activation of the protein Dishevelled via phosphorylation and 2) the activation of a heterotrimeric G protein of unknown type. Activation of Dishevelled results in the down-regulation of the Beta-Catenin destruction complex which causes ubiquitination of Beta-Catenin and its ultimate degradation via the proteasome. Inhibition of the Beta-Catenin destruction complex yields a higher cytosolic concentration of Beta-Catenin, which enters the nucleus, binds various transcriptional regulatory molecules including the TCF/LEF class of proteins, and results in the transcription of TCF/LEF target genes. Activation of the heterotrimeric G-protein pathway in turn activates Phospholipase C which in turn catalyzes the catalysis of PI(4,5)P2 into DAG and IP3. Reference: The Wnt signalling pathway. You Wnt some, you lose some: oncogenes in the Wnt signaling pathway. Wnt signaling pathway. This model is described in the article: A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways. Sivakumar KC, Dhanesh SB, Shobana S, James J, Mundayoor S. OMICS 2011 Oct; 15(10): 729-737 Abstract: The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to influence cell fate specification in the developing nervous system. Here we attempted to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Our model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E(spl)] genes and enhancement of Shh target genes by a SAG agonist that were effectively demonstrated computationally and were consistent with experimental studies. However, in the case of model simulation of Wnt and EGF pathways, the model network did not supply any concurrent results with experimental data despite the fact that drugs were added at the appropriate positions. This paves insight into the potential of crosstalks between pathways considered in our study. Therefore, we manually developed a map of signaling crosstalk, which included the species connected by representatives from Notch, Shh, Wnt, and EGF pathways and highlighted the regulation of a single target gene, Hes-1, based on drug-induced simulations. These simulations provided results that matched with experimental studies. Therefore, these signaling crosstalk models complement as a tool toward the discovery of novel regulatory processes involved in neural stem cell maintenance, proliferation, and differentiation during mammalian central nervous system development. To our knowledge, this is the first report of a simple crosstalk map that highlights the differential regulation of neural stem cell differentiation and underscores the flow of positive and negative regulatory signals modulated by drugs. This model is hosted on BioModels Database and identified by: BIOMD0000000397. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:In this study, we explored the transcriptomic consequences of strong activation of the Notch pathway in embryonic human neural stem cells and in gliomas. For this we used a forced expression of the Notch intracellular domain (NICD). Glioblastoma multiforms (GBMs) are highly vascularized brain tumors containing a subpopulation of multipotent cancer stem cells. These cells closely interact with endothelial cells in neurovascular niches. In this study we have uncovered a close link between the Notch1 pathway and the tumoral vascularization process of GBM stem cells. We observed that although the Notch1 receptor was activated, the typical target proteins (HES5, HEY1, HEY2) were not or barely expressed in two explored GBM stem cell cultures. Notch1 signalling activation by expression of the intracellular form (NICD) in these cells was found to reduce their growth rate and migration which was accompanied by the sharp reduction of neural stem cell transcription factor expression (ASCL1, OLIG2, SOX2) while HEY1/2, KLF9, SNAI2 transcription factors were upregulated. Expression of OLIG2 and growth were restored after termination of Notch1 stimulation. Remarkably, NICD expression induced the expression of pericyte cell markers (NG2, PDGFRb and a-smooth muscle actin (aSMA)) in GBM stem cells. This was paralleled with the induction of several angiogenesis-related factors most notably cytokines (HB-EGF, IL8, PLGF), metalloprotease (MMP9) and adhesion proteins (VCAM-1, ICAM-1, ITGA9). In xenotransplantation experiments, contrasting with the infiltrative and poorly-vascularized tumors obtained with control GBM stem cells, Notch1 stimulation resulted in poorly-disseminating but highly-vascularized grafts containing large vessels with lumen. Notch1-stimulated GBM cells expressed pericyte cell markers and closely associated with endothelial cells. These results reveal an important role for the Notch1 pathway in regulating GBM stem cell plasticity and angiogenic properties. Embryonic human neural progenitors obtained from Lonza, the U87 glioma cell line, and glioma cancer stem cells (Gb4 and Gb7) characterized in Guichet et al. (Glia, 2013, 61(2), 225-39) were infected with lentiviruses expressing YFP or YFP-IRES-NICD (activated form of Notch receptor). After 48h, RNA were extracted for Affymetrix microarray analysis.

Dataset Information

The protein profiles of neural stem cells

Publications

A Quantitative Proteomic Approach Explores the Possible Mechanisms by Which the Small Molecule Stemazole Promotes the Survival of Human Neural Stem Cells.

Similar Datasets

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