scholarly journals ALDH1A3 Segregated Expression and Nucleus-Associated Proteasomal Degradation Are Common Traits of Glioblastoma Stem Cells

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 7
Author(s):  
Julian Fauß ◽  
Bettina Sprang ◽  
Petra Leukel ◽  
Clemens Sommer ◽  
Teodora Nikolova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Protein Turnover ◽  
Molecular Subtypes ◽  
Glioma Cells ◽  
Subcellular Fractionation ◽  
Full Length ◽  
Glioblastoma Stem Cells ◽  
Different Types ◽  
Functional Biomarkers

Aldehyde dehydrogenase 1 isoforms A1 and A3 have been implicated as functional biomarkers associated with distinct molecular subtypes of glioblastoma and glioblastoma stem cells. However, the exact roles of these isoforms in different types of glioma cells remain unclear. The purpose of this study was to dissect the association of A1 or A3 isoforms with stem and non-stem glioblastoma cells. This study has undertaken a systematic characterization of A1 and A3 proteins in glioblastoma tissues and a panel of glioblastoma stem cells using immunocytochemical and immunofluorescence staining, Western blot and the subcellular fractionation methodology. Our main findings are (i) human GSCs express uniformly ALDH1A3 but not the ALDH1A1 isoform whereas non-stem glioma cells comparably express both isoforms; (ii) there is an abundance of ALDH1A3 peptides that prevail over the full-length form in glioblastoma stem cells but not in non-stem glioma cells; (iii) full-length ALDH1A3 and ALDH1A3 peptides are spatially segregated within the cell; and (vi) the abundance of full-length ALDH1A3 and ALDH1A3 peptides is sensitive to MG132-mediated proteasomal inhibition. Our study further supports the association of ALDH1A3 with glioblastoma stem cells and provide evidence for the regulation of ALDH1A3 activities at the level of protein turnover.

scholarly journals Characterization of Patient‐Derived Glioblastoma Stem Cells for Marker Expression, Motility, and Invasiveness

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Kyle Plusch ◽  
Alexander Stubbolo ◽  
Camryn Bernheimer ◽  
Deni S. Galileo
Keyword(s):  
Stem Cells ◽  
Glioblastoma Stem Cells ◽  
Marker Expression

scholarly journals Exploiting the Complexities of Glioblastoma Stem Cells: Insights for Cancer Initiation and Therapeutic Targeting

2020 ◽  
Vol 21 (15) ◽  
pp. 5278
Author(s):  
Joana Vieira de Castro ◽  
Céline S. Gonçalves ◽  
Adília Hormigo ◽  
Bruno M. Costa
Keyword(s):  
Stem Cells ◽  
Research Field ◽  
Tumor Type ◽  
Cell Of Origin ◽  
Glioblastoma Stem Cells ◽  
Open Questions ◽  
Cancer Initiation ◽  
Heterogeneous Nature ◽  
New Strategies

The discovery of glioblastoma stem cells (GSCs) in the 2000s revolutionized the cancer research field, raising new questions regarding the putative cell(s) of origin of this tumor type, and partly explaining the highly heterogeneous nature of glioblastoma (GBM). Increasing evidence has suggested that GSCs play critical roles in tumor initiation, progression, and resistance to conventional therapies. The remarkable oncogenic features of GSCs have generated significant interest in better defining and characterizing these cells and determining novel pathways driving GBM that could constitute attractive key therapeutic targets. While exciting breakthroughs have been achieved in the field, the characterization of GSCs is a challenge and the cell of origin of GBM remains controversial. For example, the use of several cell-surface molecular markers to identify and isolate GSCs has been a challenge. It is now widely accepted that none of these markers is, per se, sufficiently robust to distinguish GSCs from normal stem cells. Finding new strategies that are able to more efficiently and specifically target these niches could also prove invaluable against this devastating and therapy-insensitive tumor. In this review paper, we summarize the most relevant findings and discuss emerging concepts and open questions in the field of GSCs, some of which are, to some extent, pertinent to other cancer stem cells.

scholarly journals Isolation and functional characterization of human glioblastoma stem cells

2017 ◽  
Author(s):  
Xiaoyang Lan ◽  
Xiaoyang Lan ◽  
Lilian Lee ◽  
Michelle M. Kushida ◽  
Clare Che ◽  
...  
Keyword(s):  
Stem Cells ◽  
Functional Characterization ◽  
Glioblastoma Stem Cells ◽  
Human Glioblastoma

scholarly journals Mesenchymal and Proneural Subtypes of Glioblastoma Disclose Branching Based on GSC Associated Signature

2021 ◽  
Vol 22 (9) ◽  
pp. 4964
Author(s):  
Giedrius Steponaitis ◽  
Arimantas Tamasauskas
Keyword(s):  
Gene Expression ◽  
Patient Outcome ◽  
Stem Cells ◽  
Data Analysis ◽  
Clinical Data ◽  
Patient Survival ◽  
Molecular Subtypes ◽  
Glioma Stem Cells ◽  
Survival Prognosis

Glioblastomas (GBM)—the most common, therapy-resistant, and lethal tumors driven by populations of glioma stem cells (GSCs) are still on the list of the most complicated pathologies. Thus, deeper understanding and characterization of GSCs is indispensable to find suitable targets and develop more effective therapies. In the present study, we applied native glioblastoma cells and GSCs sequencing, screened for GSC-specific targets and checked if the signature is related to GBM patient pathological, clinical data as well as molecular subtypes applying TCGA cohort. Data analysis revealed that tumors of proneural and mesenchymal subtypes are branching in separate clusters based on screened gene expression. Samples of the same subtype revealed significantly different patient survival prognosis as well as recurrence chance between the clusters. Recently, different subpopulations of mesenchymal GSC demonstrating different properties were shown, which indicates possible internal heterogeneity of GBM subtypes as well. Current findings also revealed branching of molecular GBM subtypes that were significantly linked to patient outcome and that might be decided by distinct GSC subpopulations.

scholarly journals Dissecting the Effect of a 3D Microscaffold on the Transcriptome of Neural Stem Cells with Computational Approaches: A Focus on Mechanotransduction

2020 ◽  
Vol 21 (18) ◽  
pp. 6775 ◽  
Author(s):  
Federica Rey ◽  
Cecilia Pandini ◽  
Bianca Barzaghini ◽  
Letizia Messa ◽  
Toniella Giallongo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Mechanical Stimuli ◽  
Rna Seq ◽  
3D Cell Cultures ◽  
Different Types ◽  
Strongly Connected ◽  
Molecular Bases

3D cell cultures are becoming more and more important in the field of regenerative medicine due to their ability to mimic the cellular physiological microenvironment. Among the different types of 3D scaffolds, we focus on the Nichoid, a miniaturized scaffold with a structure inspired by the natural staminal niche. The Nichoid can activate cellular responses simply by subjecting the cells to mechanical stimuli. This kind of influence results in different cellular morphology and organization, but the molecular bases of these changes remain largely unknown. Through RNA-Seq approach on murine neural precursors stem cells expanded inside the Nichoid, we investigated the deregulated genes and pathways showing that the Nichoid causes alteration in genes strongly connected to mechanobiological functions. Moreover, we fully dissected this mechanism highlighting how the changes start at a membrane level, with subsequent alterations in the cytoskeleton, signaling pathways, and metabolism, all leading to a final alteration in gene expression. The results shown here demonstrate that the Nichoid influences the biological and genetic response of stem cells thorough specific alterations of cellular signaling. The characterization of these pathways elucidates the role of mechanical manipulation on stem cells, with possible implications in regenerative medicine applications.

Immunophenotypic Characterization of Human Glioblastoma Stem Cells: Correlation With Clinical Outcome

2015 ◽  
Vol 116 (5) ◽  
pp. 864-876 ◽  
Author(s):  
Gianfranca Miconi ◽  
Paola Palumbo ◽  
Soheila Raysi Dehcordi ◽  
Cristina La Torre ◽  
Francesca Lombardi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Outcome ◽  
Glioblastoma Stem Cells ◽  
Human Glioblastoma

Electron microscopic characterization of diamond thin films and substrates for diamond heteroepitaxial growth

1989 ◽  
Vol 47 ◽  
pp. 592-593
Author(s):  
J.B. Posthill ◽  
R.P. Burns ◽  
R.A. Rudder ◽  
Y.H. Lee ◽  
R.J. Markunas ◽  
...  
Keyword(s):  
Thin Films ◽  
Wide Band ◽  
Deposition Process ◽  
Heteroepitaxial Growth ◽  
Electron Microscopic ◽  
Wide Band Gap ◽  
Lattice Matching ◽  
Different Types ◽  
Diamond Thin Films

Because of diamond’s wide band gap, high thermal conductivity, high breakdown voltage and high radiation resistance, there is a growing interest in developing diamond-based devices for several new and demanding electronic applications. In developing this technology, there are several new challenges to be overcome. Much of our effort has been directed at developing a diamond deposition process that will permit controlled, epitaxial growth. Also, because of cost and size considerations, it is mandatory that a non-native substrate be developed for heteroepitaxial nucleation and growth of diamond thin films. To this end, we are currently investigating the use of Ni single crystals on which different types of epitaxial metals are grown by molecular beam epitaxy (MBE) for lattice matching to diamond as well as surface chemistry modification. This contribution reports briefly on our microscopic observations that are integral to these endeavors.

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