scholarly journals Meta-analysis of whole-genome gene expression datasets assessing the effects of IDH1 and IDH2 mutations in isogenic disease models

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Hans-Juergen Schulten ◽  
Fatima Al-Adwani ◽  
Haneen A. Bin Saddeq ◽  
Heba Alkhatabi ◽  
Nofe Alganmi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Glioma Cells ◽  
Heart Tissue ◽  
Disease Models ◽  
Signal Molecules ◽  
Mouse Heart ◽  
Idh Mutations

AbstractMutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are oncogenic drivers to a variable extent in several tumors, including gliomas, acute myeloid leukemia (AML), cholangiocarcinoma, melanoma, and thyroid carcinoma. The pathobiological effects of these mutations vary considerably, impeding the identification of common expression profiles. We performed an expression meta-analysis between IDH-mutant (IDHmut) and IDH-wild-type (IDHwt) conditions in six human and mouse isogenic disease models. The datasets included colon cancer cells, glioma cells, heart tissue, hepatoblasts, and neural stem cells. Among differentially expressed genes (DEGs), serine protease 23 (PRSS23) was upregulated in four datasets, i.e., in human colon carcinoma cells, mouse heart tissue, mouse neural stem cells, and human glioma cells. Carbonic anhydrase 2 (CA2) and prolyl 3-hydroxylase 2 (P3H2) were upregulated in three datasets, and SOX2 overlapping transcript (SOX2-OT) was downregulated in three datasets. The most significantly overrepresented protein class was termed intercellular signal molecules. An additional DEG set contained genes that were both up- and downregulated in different datasets and included oxidases and extracellular matrix structural proteins as the most significantly overrepresented protein classes. In conclusion, this meta-analysis provides a comprehensive overview of the expression effects of IDH mutations shared between different isogenic disease models. The generated dataset includes biomarkers, e.g., PRSS23 that may gain relevance for further research or clinical applications in IDHmut tumors.

Multimodal Actions of Neural Stem Cells in a Mouse Model of ALS: A Meta-Analysis

2012 ◽  
Vol 4 (165) ◽  
pp. 165ra164-165ra164 ◽  
Author(s):  
Y. D. Teng ◽  
S. C. Benn ◽  
S. N. Kalkanis ◽  
J. M. Shefner ◽  
R. C. Onario ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mouse Model ◽  
Neural Stem Cells ◽  
Meta Analysis

scholarly journals Do Neural Stem Cells Have a Choice? Heterogenic Outcome of Cell Fate Acquisition in Different Injury Models

2019 ◽  
Vol 20 (2) ◽  
pp. 455 ◽  
Author(s):  
Felix Beyer ◽  
Iria Samper Agrelo ◽  
Patrick Küry
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Ex Vivo ◽  
Meta Analysis ◽  
Cell Types ◽  
Adult Brain ◽  
Repair Capacity ◽  
Cell Fate Decisions ◽  
Limiting Parameters

The adult mammalian central nervous system (CNS) is generally considered as repair restricted organ with limited capacities to regenerate lost cells and to successfully integrate them into damaged nerve tracts. Despite the presence of endogenous immature cell types that can be activated upon injury or in disease cell replacement generally remains insufficient, undirected, or lost cell types are not properly generated. This limitation also accounts for the myelin repair capacity that still constitutes the default regenerative activity at least in inflammatory demyelinating conditions. Ever since the discovery of endogenous neural stem cells (NSCs) residing within specific niches of the adult brain, as well as the description of procedures to either isolate and propagate or artificially induce NSCs from various origins ex vivo, the field has been rejuvenated. Various sources of NSCs have been investigated and applied in current neuropathological paradigms aiming at the replacement of lost cells and the restoration of functionality based on successful integration. Whereas directing and supporting stem cells residing in brain niches constitutes one possible approach many investigations addressed their potential upon transplantation. Given the heterogeneity of these studies related to the nature of grafted cells, the local CNS environment, and applied implantation procedures we here set out to review and compare their applied protocols in order to evaluate rate-limiting parameters. Based on our compilation, we conclude that in healthy CNS tissue region specific cues dominate cell fate decisions. However, although increasing evidence points to the capacity of transplanted NSCs to reflect the regenerative need of an injury environment, a still heterogenic picture emerges when analyzing transplantation outcomes in injury or disease models. These are likely due to methodological differences despite preserved injury environments. Based on this meta-analysis, we suggest future NSC transplantation experiments to be conducted in a more comparable way to previous studies and that subsequent analyses must emphasize regional heterogeneity such as accounting for differences in gray versus white matter.

The Expression Profiles of lncRNAs and Their Regulatory Network During Smek1/2 Knockout Mouse Neural Stem Cells Differentiation

2020 ◽  
Vol 15 (1) ◽  
pp. 77-88 ◽  
Author(s):  
Qichang Yang ◽  
Jing Wu ◽  
Jian Zhao ◽  
Tianyi Xu ◽  
Ping Han ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Wildtype Mouse ◽  
Pathway Network ◽  
Differentiation And Proliferation

Background: Previous studies indicated that the cell fate of neural stem cells (NSCs) after differentiation is determined by Smek1, one isoform of suppressor of Mek null (Smek). Smek deficiency prevents NSCs from differentiation, thus affects the development of nervous system. In recent years, lncRNAs have been found to participate in numerous developmental and biological pathways. However, the effects of knocking out Smek on the expression profiles of lncRNAs during the differentiation remain unknown. Objective: This study is to explore the expression profiles of lncRNAs and their possible function during the differentiation from Smek1/2 knockout NSCs. Methods: We obtained NSCs from the C57BL/6J mouse fetal cerebral cortex. One group of NSCs was from wildtype mouse (WT group), while another group was from knocked out Smek1/2 (KO group). Results: By analyzing the RNA-Seq data, we found that after knocking out Smek1/2, the expression profiles of mRNAs and lncRNAs revealed significant changes. Analyses indicated that these affected mRNAs have connections with the pathway network for the differentiation and proliferation of NSCs. Furthermore, we performed a co-expression network analysis on the differentially expressed mRNAs and lncRNAs, which helped reveal the possible regulatory rules of lncRNAs during the differentiation after knocking out Smek1/2. Conclusion: By comparing group WT with KO, we found 366 differentially expressed mRNAs and 12 lncRNAs. GO and KEGG enrichment analysis on these mRNAs suggested their relationships with differentiation and proliferation of NSCs. Some of these mRNAs and lncRNAs have been verified to play regulatory roles in nervous system. Analyses on the co-expression network also indicated the possible functions of affected mRNAs and lncRNAs during NSCs differentiation after knocking out Smek1/2.

scholarly journals The inhibiting effect of neural stem cells on proliferation and invasion of glioma cells

Oncotarget ◽  
2017 ◽  
Vol 8 (44) ◽  
pp. 76949-76960 ◽  
Author(s):  
Jing An ◽  
Hanqi Yan ◽  
Xingxing Li ◽  
Ruolan Tan ◽  
Xinlin Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Glioma Cells ◽  
Inhibiting Effect ◽  
Proliferation And Invasion

scholarly journals Circular RNA expression profiles during the differentiation of mouse neural stem cells

2018 ◽  
Vol 12 (S8) ◽  
Author(s):  
Qichang Yang ◽  
Jing Wu ◽  
Jian Zhao ◽  
Tianyi Xu ◽  
Zhongming Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Expression Profiles ◽  
Circular Rna ◽  
Rna Expression

scholarly journals Transmigration of Neural Stem Cells across the Blood Brain Barrier Induced by Glioma Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e60655 ◽  
Author(s):  
Mónica Díaz-Coránguez ◽  
José Segovia ◽  
Adolfo López-Ornelas ◽  
Henry Puerta-Guardo ◽  
Juan Ludert ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Blood Brain Barrier ◽  
Glioma Cells ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Inactivation of the ATMIN/ATM pathway protects against glioblastoma formation

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Sophia M Blake ◽  
Stefan H Stricker ◽  
Hanna Halavach ◽  
Anna R Poetsch ◽  
George Cresswell ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Neural Development ◽  
Combined Treatment ◽  
Glioma Cells ◽  
Wild Type ◽  
Genetic Inactivation ◽  
Primary Glioma ◽  
Human Gbm ◽  
Atm Signaling

Glioblastoma multiforme (GBM) is the most aggressive human primary brain cancer. Using a Trp53-deficient mouse model of GBM, we show that genetic inactivation of the Atm cofactor Atmin, which is dispensable for embryonic and adult neural development, strongly suppresses GBM formation. Mechanistically, expression of several GBM-associated genes, including Pdgfra, was normalized by Atmin deletion in the Trp53-null background. Pharmacological ATM inhibition also reduced Pdgfra expression, and reduced the proliferation of Trp53-deficient primary glioma cells from murine and human tumors, while normal neural stem cells were unaffected. Analysis of GBM datasets showed that PDGFRA expression is also significantly increased in human TP53-mutant compared with TP53-wild-type tumors. Moreover, combined treatment with ATM and PDGFRA inhibitors efficiently killed TP53-mutant primary human GBM cells, but not untransformed neural stem cells. These results reveal a new requirement for ATMIN-dependent ATM signaling in TP53-deficient GBM, indicating a pro-tumorigenic role for ATM in the context of these tumors.

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