Transcriptomic analysis of neural stem and progenitor cells in comparison with glioblastoma stem cells

Introduction. There is currently no effective therapy for the treatment of glioblastoma. This is partly explained by the high degree of intra- and intertumor heterogeneity of GB, the source of which is believed to be glioblastoma stem cells (GSC). The question of the origin of GSC, which is importan...

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Main Authors: V. E. Shevchenko, N. E.  Arnotskaya, T.  I. Kushnir, A. S. Bryukhovetskiy
Format: Article
Language:Russian
Published: ABV-press 2023-12-01
Series:Успехи молекулярной онкологии
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Online Access:https://umo.abvpress.ru/jour/article/view/615
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author V. E. Shevchenko
N. E.  Arnotskaya
T.  I. Kushnir
A. S. Bryukhovetskiy
author_facet V. E. Shevchenko
N. E.  Arnotskaya
T.  I. Kushnir
A. S. Bryukhovetskiy
author_sort V. E. Shevchenko
collection DOAJ
description Introduction. There is currently no effective therapy for the treatment of glioblastoma. This is partly explained by the high degree of intra- and intertumor heterogeneity of GB, the source of which is believed to be glioblastoma stem cells (GSC). The question of the origin of GSC, which is important for improving clinical outcomes, still remains open. It is believed that GSCs can be formed as a result of oncogenic transformation of neural stem and progenitor cells (NSPcs), which have morphological and functional properties similar to them. Despite significant progress in elucidating the nature of GSCs, little is yet known about the specifically expressed genes and transcripts in these cells in comparison with NSPcs. In this regard, it becomes relevant to study the molecular mechanisms of gliomagenesis using model cell systems based on various clones of GSC.Aim. To conduct a comparative transcriptomic analysis of CD133+-NSPCs and CD133+-GSCs to study the molecular genetic differences between the phenotypes of these cells and identify potential targets for therapeutic effects on GSCs.Materials and methods. Used: highly sensitive transcriptomic analysis on high-density microarrays, cellular technologies, modern bioinformatics analysis.Results. Transcriptomic analysis of CD133+-GSCs and CD133+-NSPCs identified 1825 differentially expressed genes. The biological processes and signaling cascades activated in CD133+-GSCs have been established. It was shown that significant transcriptomic aberrations in CD133+-GSC compared to CD133+-NSPC are primarily due to a group of transcripts regulated by the Shh (Sonic hedgehog), mTOR (mammalian target of rapamycin), ALK (anaplastic lymphoma kinase) signaling cascades, transcription factors E2F1, PRC2, HOXA9, MYC, as well as oncogenes ERBB2 and KRAS. Six transcripts (AQP9, TOX15, HOXB2, STEAP3, TREM1, RFC2) highly expressed in CD133+-GSC and closely associated with the survival of patients with glioblastoma, which may be potential targets for therapeutic effects on CD133+-GSC associated with gliomagenesis, which may be potential targets for therapeutic effects on CD133+-GSC, have been identified and annotated.Conclusion. The data obtained indicate a number of significant molecular genetic differences between the two cell phenotypes, which can be used in the development of new therapeutic approaches for the treatment of glioblastoma.
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spelling doaj-art-ecdc85f70f9a42aaabc8e307610f7e102025-08-20T03:00:54ZrusABV-pressУспехи молекулярной онкологии2313-805X2413-37872023-12-0110413714810.17650/2313-805X-2023-10-4-137-148312Transcriptomic analysis of neural stem and progenitor cells in comparison with glioblastoma stem cellsV. E. Shevchenko0N. E.  Arnotskaya1T.  I. Kushnir2A. S. Bryukhovetskiy3N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaClinical Hospital “NeuroVita”Introduction. There is currently no effective therapy for the treatment of glioblastoma. This is partly explained by the high degree of intra- and intertumor heterogeneity of GB, the source of which is believed to be glioblastoma stem cells (GSC). The question of the origin of GSC, which is important for improving clinical outcomes, still remains open. It is believed that GSCs can be formed as a result of oncogenic transformation of neural stem and progenitor cells (NSPcs), which have morphological and functional properties similar to them. Despite significant progress in elucidating the nature of GSCs, little is yet known about the specifically expressed genes and transcripts in these cells in comparison with NSPcs. In this regard, it becomes relevant to study the molecular mechanisms of gliomagenesis using model cell systems based on various clones of GSC.Aim. To conduct a comparative transcriptomic analysis of CD133+-NSPCs and CD133+-GSCs to study the molecular genetic differences between the phenotypes of these cells and identify potential targets for therapeutic effects on GSCs.Materials and methods. Used: highly sensitive transcriptomic analysis on high-density microarrays, cellular technologies, modern bioinformatics analysis.Results. Transcriptomic analysis of CD133+-GSCs and CD133+-NSPCs identified 1825 differentially expressed genes. The biological processes and signaling cascades activated in CD133+-GSCs have been established. It was shown that significant transcriptomic aberrations in CD133+-GSC compared to CD133+-NSPC are primarily due to a group of transcripts regulated by the Shh (Sonic hedgehog), mTOR (mammalian target of rapamycin), ALK (anaplastic lymphoma kinase) signaling cascades, transcription factors E2F1, PRC2, HOXA9, MYC, as well as oncogenes ERBB2 and KRAS. Six transcripts (AQP9, TOX15, HOXB2, STEAP3, TREM1, RFC2) highly expressed in CD133+-GSC and closely associated with the survival of patients with glioblastoma, which may be potential targets for therapeutic effects on CD133+-GSC associated with gliomagenesis, which may be potential targets for therapeutic effects on CD133+-GSC, have been identified and annotated.Conclusion. The data obtained indicate a number of significant molecular genetic differences between the two cell phenotypes, which can be used in the development of new therapeutic approaches for the treatment of glioblastoma.https://umo.abvpress.ru/jour/article/view/615glioblastomaglioblastoma stem cellsneural stem cellsprogenitor cellstranscriptomics
spellingShingle V. E. Shevchenko
N. E.  Arnotskaya
T.  I. Kushnir
A. S. Bryukhovetskiy
Transcriptomic analysis of neural stem and progenitor cells in comparison with glioblastoma stem cells
Успехи молекулярной онкологии
glioblastoma
glioblastoma stem cells
neural stem cells
progenitor cells
transcriptomics
title Transcriptomic analysis of neural stem and progenitor cells in comparison with glioblastoma stem cells
title_full Transcriptomic analysis of neural stem and progenitor cells in comparison with glioblastoma stem cells
title_fullStr Transcriptomic analysis of neural stem and progenitor cells in comparison with glioblastoma stem cells
title_full_unstemmed Transcriptomic analysis of neural stem and progenitor cells in comparison with glioblastoma stem cells
title_short Transcriptomic analysis of neural stem and progenitor cells in comparison with glioblastoma stem cells
title_sort transcriptomic analysis of neural stem and progenitor cells in comparison with glioblastoma stem cells
topic glioblastoma
glioblastoma stem cells
neural stem cells
progenitor cells
transcriptomics
url https://umo.abvpress.ru/jour/article/view/615
work_keys_str_mv AT veshevchenko transcriptomicanalysisofneuralstemandprogenitorcellsincomparisonwithglioblastomastemcells
AT nearnotskaya transcriptomicanalysisofneuralstemandprogenitorcellsincomparisonwithglioblastomastemcells
AT tikushnir transcriptomicanalysisofneuralstemandprogenitorcellsincomparisonwithglioblastomastemcells
AT asbryukhovetskiy transcriptomicanalysisofneuralstemandprogenitorcellsincomparisonwithglioblastomastemcells