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Astrocytes derived from trisomic human embryonic stem cells express markers of astrocytic cancer cells and premalignant stem-like progenitors

BACKGROUND: Trisomic variants of human embryonic stem cells (hESCs) arise spontaneously in culture. Although trisomic hESCs share many properties with diploid hESCs, they also exhibit features of cancer stem cells. Since most hESC-based therapies will utilize differentiated derivatives, it is impera...

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Autores principales: Gopalakrishna-Pillai, Sailesh, Iverson, Linda E
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873256/
https://www.ncbi.nlm.nih.gov/pubmed/20423517
http://dx.doi.org/10.1186/1755-8794-3-12
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author Gopalakrishna-Pillai, Sailesh
Iverson, Linda E
author_facet Gopalakrishna-Pillai, Sailesh
Iverson, Linda E
author_sort Gopalakrishna-Pillai, Sailesh
collection PubMed
description BACKGROUND: Trisomic variants of human embryonic stem cells (hESCs) arise spontaneously in culture. Although trisomic hESCs share many properties with diploid hESCs, they also exhibit features of cancer stem cells. Since most hESC-based therapies will utilize differentiated derivatives, it is imperative to investigate the potential of trisomic hESCs to undergo malignant transformation during differentiation prior to their use in the clinical setting. METHODS: Diploid and trisomic hESCs were differentiated into astrocytic progenitors cells (APCs), RNA extracted and hybridized to human exon-specific microarrays. Global gene expression profiles of diploid and trisomic APCs were compared to that of an astrocytoma cell line and glioblastoma samples, analyzed by others, using the same microarray platform. RESULTS: Bioinformatic analysis of microarray data indicates that differentiated trisomic APCs exhibit global expression profiles with similarities to the malignant astrocytoma cell line. An analogous trend is observed in comparison to glioblastoma samples indicating that trisomic APCs express markers of astrocytic cancer cells. The analysis also allowed identification of transcripts predicted to be differentially expressed in brain tumor stem cells. These data indicate that in vitro differentiation of trisomic hESCs along astrocytic pathways give rise to cells exhibiting properties of premalignant astrocytic stem/progenitor cells. CONCLUSIONS: Given their occult nature, opportunities to study premalignant stem/progenitor cells in human have been few. The ability to propagate and direct the differentiation of aneuploid hESCs provides a powerful in vitro system for investigating biological properties of human cells exhibiting features of premalignant stem cells. This in vitro culture system can be used to elucidate changes in gene expression occurring enroute to malignant transformation and to identify molecular markers of cancer stem/progenitor cells. These markers are invaluable for diagnostic purposes and may be novel targets for therapeutic intervention.
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spelling pubmed-28732562010-05-20 Astrocytes derived from trisomic human embryonic stem cells express markers of astrocytic cancer cells and premalignant stem-like progenitors Gopalakrishna-Pillai, Sailesh Iverson, Linda E BMC Med Genomics Research article BACKGROUND: Trisomic variants of human embryonic stem cells (hESCs) arise spontaneously in culture. Although trisomic hESCs share many properties with diploid hESCs, they also exhibit features of cancer stem cells. Since most hESC-based therapies will utilize differentiated derivatives, it is imperative to investigate the potential of trisomic hESCs to undergo malignant transformation during differentiation prior to their use in the clinical setting. METHODS: Diploid and trisomic hESCs were differentiated into astrocytic progenitors cells (APCs), RNA extracted and hybridized to human exon-specific microarrays. Global gene expression profiles of diploid and trisomic APCs were compared to that of an astrocytoma cell line and glioblastoma samples, analyzed by others, using the same microarray platform. RESULTS: Bioinformatic analysis of microarray data indicates that differentiated trisomic APCs exhibit global expression profiles with similarities to the malignant astrocytoma cell line. An analogous trend is observed in comparison to glioblastoma samples indicating that trisomic APCs express markers of astrocytic cancer cells. The analysis also allowed identification of transcripts predicted to be differentially expressed in brain tumor stem cells. These data indicate that in vitro differentiation of trisomic hESCs along astrocytic pathways give rise to cells exhibiting properties of premalignant astrocytic stem/progenitor cells. CONCLUSIONS: Given their occult nature, opportunities to study premalignant stem/progenitor cells in human have been few. The ability to propagate and direct the differentiation of aneuploid hESCs provides a powerful in vitro system for investigating biological properties of human cells exhibiting features of premalignant stem cells. This in vitro culture system can be used to elucidate changes in gene expression occurring enroute to malignant transformation and to identify molecular markers of cancer stem/progenitor cells. These markers are invaluable for diagnostic purposes and may be novel targets for therapeutic intervention. BioMed Central 2010-04-27 /pmc/articles/PMC2873256/ /pubmed/20423517 http://dx.doi.org/10.1186/1755-8794-3-12 Text en Copyright ©2010 Gopalakrishna-Pillai and Iverson; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research article
Gopalakrishna-Pillai, Sailesh
Iverson, Linda E
Astrocytes derived from trisomic human embryonic stem cells express markers of astrocytic cancer cells and premalignant stem-like progenitors
title Astrocytes derived from trisomic human embryonic stem cells express markers of astrocytic cancer cells and premalignant stem-like progenitors
title_full Astrocytes derived from trisomic human embryonic stem cells express markers of astrocytic cancer cells and premalignant stem-like progenitors
title_fullStr Astrocytes derived from trisomic human embryonic stem cells express markers of astrocytic cancer cells and premalignant stem-like progenitors
title_full_unstemmed Astrocytes derived from trisomic human embryonic stem cells express markers of astrocytic cancer cells and premalignant stem-like progenitors
title_short Astrocytes derived from trisomic human embryonic stem cells express markers of astrocytic cancer cells and premalignant stem-like progenitors
title_sort astrocytes derived from trisomic human embryonic stem cells express markers of astrocytic cancer cells and premalignant stem-like progenitors
topic Research article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873256/
https://www.ncbi.nlm.nih.gov/pubmed/20423517
http://dx.doi.org/10.1186/1755-8794-3-12
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