The necessity for standardization of glioma stem cell culture: a systematic review

Zhang, Lei; Yu, Hao; Yuan, Yuhui; Yu, John S.; Lou, Zhenkun; Xue, Yixue; Liu, Yunhui

doi:10.1186/s13287-020-01589-8

Cited by 15 publications

(7 citation statements)

References 70 publications

(97 reference statements)

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“…In GBM, the isolation and characterization of GSCs have been carried out by culturing primary tumor cells under neural stem cells serum-free media conditions 30 . However, there have been inconsistencies concerning the GSC model due to the lack of consensus on culture methods and specific GSC markers used among different research groups 31 . Based on the original concept of the embryonal origin of cancer, we analyzed publicly-available scRNA-seq data from GBM patients (n=28) 14 searching for undifferentiated cells harboring ESC-like signatures within the tumor mass.…”

Section: Resultsmentioning

confidence: 99%

Glioblastoma embryonic-like stem cells exhibit immune-evasive phenotype

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Ensenat³

et al. 2021

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Glioma stem cells (GSCs) are a subset of cells with self-renewal and tumor-initiating capacities that are thought to participate in drug resistance and immune evasion mechanisms in glioblastoma (GBM). Given GBM heterogeneity, we hypothesized that GSCs might also display cellular hierarchies associated with different degrees of stemness. We evaluated a single-cell RNA-seq glioblastoma dataset (n = 28) and identified a stem cell population co-expressing high levels of embryonic pluripotency markers, named core glioma stem cells (c-GSCs). This embryonic-like population represents 4.22% of the tumor cell mass, and pathway analysis revealed an upregulation of stemness and downregulation of immune-associated pathways. Using induced pluripotent stem cell technology, we generated an in vitro model of c-GSCs by reprogramming glioblastoma patient-derived cells into induced c-GSCs (ic-GSCs). Immunostaining of ic-GSCs showed high expression of embryonic pluripotency markers and downregulation of antigen presentation HLA proteins, mimicking its tumoral counterpart. Transcriptomic analysis revealed a strong agreement of enriched biological pathways between tumor c-GSCs and in vitro ic-GSCs (k = 0.71). Integration of ic-GSC DNA methylation and gene expression with chromatin state analysis of epigenomic maps (n = 833) indicated that polycomb repressive marks downregulate HLA genes in stem-like phenotype. Together, we identified c-GSCs as a GBM cell population with embryonic signatures and poor immunogenicity. Genome-scale transcriptomic and epigenomic profiling provide a valuable resource for studying immune evasion mechanisms governing c-GSCs and identifying potential therapeutic targets for GBM immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Glioblastoma embryonic-like stem cells exhibit immune-evasive phenotype

Sesé

Iñiguez

Ensenat³

et al. 2021

Preprint

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“…It is known that GSCs are responsible for cancer progression and recurrence, and the elimination of GSCs is crucial for treating glioblastoma ( 38 , 39 ). To the best of our knowledge, the association between GASC1 expression and the clinical progression of glioma remains unknown.…”

Section: Discussionmentioning

confidence: 99%

GASC1 promotes glioma progression by enhancing NOTCH1 signaling

et al. 2021

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Recent studies have reported that gene amplified in squamous cell carcinoma 1 (GASC1) is involved in the progression of several types of cancer. However, whether GASC1 promotes glioma progression remains unknown. Therefore, the present study aimed to investigate the effect of GASC1 exposure on glioma tumorigenesis. The western blot demonstrated that grade III and IV glioma tissues exhibited a higher mRNA and protein expression of GASC1. Moreover, CD133 + U87 or U251 cells from magnetic cell separation exhibited a higher GASC1 expression. Invasion Transwell assay, clonogenic assay and wound healing assay have shown that GASC1 inhibition using a pharmacological inhibitor and specific short hairpin (sh)RNA suppressed the invasive, migratory and tumorsphere forming abilities of primary culture human glioma cells. Furthermore, GASC1-knockdown decreased notch receptor (Notch) responsive protein hes family bHLH transcription factor 1 (Hes1) signaling. GASC1 inhibition reduced notch receptor 1 (NOTCH1) expression, and a NOTCH1 inhibitor enhanced the effects of GASC1 inhibition on the CD133 + U87 or U251 cell tumorsphere forming ability, while NOTCH1 overexpression abrogated these effects. In addition, the GASC1 inhibitor caffeic acid and/or the NOTCH1 inhibitor DAPT (a γ-Secretase Inhibitor), efficiently suppressed the human glioma xenograft tumors. Thus, the present results demonstrated the importance of GASC1 in the progression of glioma and identified that GASC1 promotes glioma progression, at least in part, by enhancing NOTCH signaling, suggesting that GASC1/NOTCH1 signaling may be a potential therapeutic target for glioma treatment.

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“…( 21 ) and Zhang et al. ( 22 ). Dissociated U87, U251, and GL261 cells were washed twice with phosphate-buffered saline (PBS, pH 7.2) to eliminate FBS and then resuspended in serum-free DMEM/F-12 medium (Gibco, USA) supplemented with basic fibroblast growth factor (bFGF, 20 ng/ml, Peprotech), epidermal growth factor (EGF, 20 ng/ml, Peprotech, USA), and 2% B27 (Life Technologies Corporation, Grand Island, NY, USA).…”

Section: Methodsmentioning

confidence: 97%

P4HA1 Regulates CD31 via COL6A1 in the Transition of Glioblastoma Stem-Like Cells to Tumor Endothelioid Cells

et al. 2022

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Glioblastoma multiforme (GBM) is a common intracranial malignancy characterized by abundant and aberrant vasculature. The efficiency of existing antivascular treatments remains unsatisfactory. The transition of glioblastoma stem-like cells (GSCs) into tumor endothelioid cells (ECs) has been thought to cause glioma neovascularization and anti-angiogenesis tolerance, but the mechanisms regulating glioma transdifferentiation remains unclear. Our previous study found that P4HA1 regulates GSCs vascular mimicry in a hypoxic microenvironment, but the detailed molecular mechanism has not been determined. In this study, candidate protein COL6A1 was screened by mass spectrometry. In vitro experiments show that P4HA1 regulates the expression of CD31 via COL6A1, with the levels of expression of P4HA1, COL6A1 and the vascular endothelial molecular markers CD31 showing positive correlations in vivo assay. Altering the expression of P4HA1 in GSCs altered the expression of COL6A1 and CD31, thereby inducing glioma angiogenesis. In conclusion, this study revealed that the P4HA1/COL6A1 axis modulates the transdifferentiation process of GSCs into ECs. Interrupting this signaling axis can inhibit glioma angiogenesis, suggesting that this axis may be a novel target for antivascular therapy in patients with glioma.

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The necessity for standardization of glioma stem cell culture: a systematic review

Cited by 15 publications

References 70 publications

Glioblastoma embryonic-like stem cells exhibit immune-evasive phenotype

Glioblastoma embryonic-like stem cells exhibit immune-evasive phenotype

GASC1 promotes glioma progression by enhancing NOTCH1 signaling

P4HA1 Regulates CD31 via COL6A1 in the Transition of Glioblastoma Stem-Like Cells to Tumor Endothelioid Cells

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