Transcriptional Differences between Normal and Glioma-Derived Glial Progenitor Cells Identify a Core Set of Dysregulated Genes

Romane M. Auvergne; Fraser J. Sim; Su Wang; Devin Chandler-Militello; Jaclyn Burch; Yazan AlFanek; Danielle Davis; Abdellatif Benraiss; Kevin Walter; Pragathi Achanta; Mahlon Johnson; Alfredo Quinones-Hinojosa; Sridaran Natesan; Heide L. Ford; Steven A. Goldman

doi:10.1016/j.celrep.2013.04.035

Transcriptional Differences between Normal and Glioma-Derived Glial Progenitor Cells Identify a Core Set of Dysregulated Genes

Romane M. Auvergne, Fraser J. Sim, Su Wang, Devin Chandler-Militello, Jaclyn Burch, Yazan AlFanek, Danielle Davis, Abdellatif Benraiss, Kevin Walter, Pragathi Achanta, Mahlon Johnson, Alfredo Quinones-Hinojosa, Sridaran Natesan, Heide L. Ford, Steven A. Goldman

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

Abstract

Glial progenitor cells (GPCs) are a potential source of malignant gliomas. We used A2B5-based sorting to extract tumorigenic GPCs from human gliomas spanning World Health Organization grades II-IV. Messenger RNA profiling identified a cohort of genes that distinguished A2B5⁺ glioma tumor progenitor cells (TPCs) from A2B5⁺ GPCs isolated from normal white matter. A core set of genes and pathways was substantially dysregulated in A2B5⁺ TPCs, which included the transcription factor SIX1 and its principal cofactors, EYA1 and DACH2. Small hairpin RNAi silencing of SIX1 inhibited the expansion of glioma TPCs invitro and invivo, suggesting a critical and unrecognized role of the SIX1-EYA1-DACH2 system in glioma genesis or progression. By comparing the expression patterns of glioma TPCs with those of normal GPCs, we have identified a discrete set of pathways by which glial tumorigenesis may be better understood and more specifically targeted.

Original language	English (US)
Pages (from-to)	2127-2141
Number of pages	15
Journal	Cell Reports
Volume	3
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2013.04.035
State	Published - Mar 27 2013
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2013.04.035

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Auvergne, R. M., Sim, F. J., Wang, S., Chandler-Militello, D., Burch, J., AlFanek, Y., Davis, D., Benraiss, A., Walter, K., Achanta, P., Johnson, M., Quinones-Hinojosa, A., Natesan, S., Ford, H. L., & Goldman, S. A. (2013). Transcriptional Differences between Normal and Glioma-Derived Glial Progenitor Cells Identify a Core Set of Dysregulated Genes. Cell Reports, 3(6), 2127-2141. https://doi.org/10.1016/j.celrep.2013.04.035

Auvergne, RM, Sim, FJ, Wang, S, Chandler-Militello, D, Burch, J, AlFanek, Y, Davis, D, Benraiss, A, Walter, K, Achanta, P, Johnson, M, Quinones-Hinojosa, A, Natesan, S, Ford, HL & Goldman, SA 2013, 'Transcriptional Differences between Normal and Glioma-Derived Glial Progenitor Cells Identify a Core Set of Dysregulated Genes', Cell Reports, vol. 3, no. 6, pp. 2127-2141. https://doi.org/10.1016/j.celrep.2013.04.035

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title = "Transcriptional Differences between Normal and Glioma-Derived Glial Progenitor Cells Identify a Core Set of Dysregulated Genes",

abstract = "Glial progenitor cells (GPCs) are a potential source of malignant gliomas. We used A2B5-based sorting to extract tumorigenic GPCs from human gliomas spanning World Health Organization grades II-IV. Messenger RNA profiling identified a cohort of genes that distinguished A2B5+ glioma tumor progenitor cells (TPCs) from A2B5+ GPCs isolated from normal white matter. A core set of genes and pathways was substantially dysregulated in A2B5+ TPCs, which included the transcription factor SIX1 and its principal cofactors, EYA1 and DACH2. Small hairpin RNAi silencing of SIX1 inhibited the expansion of glioma TPCs invitro and invivo, suggesting a critical and unrecognized role of the SIX1-EYA1-DACH2 system in glioma genesis or progression. By comparing the expression patterns of glioma TPCs with those of normal GPCs, we have identified a discrete set of pathways by which glial tumorigenesis may be better understood and more specifically targeted.",

author = "Auvergne, {Romane M.} and Sim, {Fraser J.} and Su Wang and Devin Chandler-Militello and Jaclyn Burch and Yazan AlFanek and Danielle Davis and Abdellatif Benraiss and Kevin Walter and Pragathi Achanta and Mahlon Johnson and Alfredo Quinones-Hinojosa and Sridaran Natesan and Ford, {Heide L.} and Goldman, {Steven A.}",

note = "Funding Information: We thank Webster Pilcher, Howard Silberstein, and Edward Vates for arranging tissue donation; Adam Cornwell for advice on genomics analysis; and Tricia Protack, Adam Cornwell, Matthew J. Kaule, Alex Zielke, Xiaojie Li, Marissa Dombovy-Johnson, and Andrew Bennett for technical assistance. This work was supported by grants from the Miriam and Sheldon G. Adelson Medical Research Foundation, the New York State Stem Cell Research Board, the James S. McDonnell Science Foundation, Sanofi-Aventis, and National Institute of Neurological Disorders and Stroke (K08NS055851 to A.Q.-H. and R01NS75345 and R01NS39559 to S.A.G.). ",

year = "2013",

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doi = "10.1016/j.celrep.2013.04.035",

language = "English (US)",

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AU - Auvergne, Romane M.

AU - Sim, Fraser J.

AU - Wang, Su

AU - Chandler-Militello, Devin

AU - Burch, Jaclyn

AU - AlFanek, Yazan

AU - Davis, Danielle

AU - Benraiss, Abdellatif

AU - Walter, Kevin

AU - Achanta, Pragathi

AU - Johnson, Mahlon

AU - Quinones-Hinojosa, Alfredo

AU - Natesan, Sridaran

AU - Ford, Heide L.

AU - Goldman, Steven A.

N1 - Funding Information: We thank Webster Pilcher, Howard Silberstein, and Edward Vates for arranging tissue donation; Adam Cornwell for advice on genomics analysis; and Tricia Protack, Adam Cornwell, Matthew J. Kaule, Alex Zielke, Xiaojie Li, Marissa Dombovy-Johnson, and Andrew Bennett for technical assistance. This work was supported by grants from the Miriam and Sheldon G. Adelson Medical Research Foundation, the New York State Stem Cell Research Board, the James S. McDonnell Science Foundation, Sanofi-Aventis, and National Institute of Neurological Disorders and Stroke (K08NS055851 to A.Q.-H. and R01NS75345 and R01NS39559 to S.A.G.).

PY - 2013/3/27

Y1 - 2013/3/27

N2 - Glial progenitor cells (GPCs) are a potential source of malignant gliomas. We used A2B5-based sorting to extract tumorigenic GPCs from human gliomas spanning World Health Organization grades II-IV. Messenger RNA profiling identified a cohort of genes that distinguished A2B5+ glioma tumor progenitor cells (TPCs) from A2B5+ GPCs isolated from normal white matter. A core set of genes and pathways was substantially dysregulated in A2B5+ TPCs, which included the transcription factor SIX1 and its principal cofactors, EYA1 and DACH2. Small hairpin RNAi silencing of SIX1 inhibited the expansion of glioma TPCs invitro and invivo, suggesting a critical and unrecognized role of the SIX1-EYA1-DACH2 system in glioma genesis or progression. By comparing the expression patterns of glioma TPCs with those of normal GPCs, we have identified a discrete set of pathways by which glial tumorigenesis may be better understood and more specifically targeted.

AB - Glial progenitor cells (GPCs) are a potential source of malignant gliomas. We used A2B5-based sorting to extract tumorigenic GPCs from human gliomas spanning World Health Organization grades II-IV. Messenger RNA profiling identified a cohort of genes that distinguished A2B5+ glioma tumor progenitor cells (TPCs) from A2B5+ GPCs isolated from normal white matter. A core set of genes and pathways was substantially dysregulated in A2B5+ TPCs, which included the transcription factor SIX1 and its principal cofactors, EYA1 and DACH2. Small hairpin RNAi silencing of SIX1 inhibited the expansion of glioma TPCs invitro and invivo, suggesting a critical and unrecognized role of the SIX1-EYA1-DACH2 system in glioma genesis or progression. By comparing the expression patterns of glioma TPCs with those of normal GPCs, we have identified a discrete set of pathways by which glial tumorigenesis may be better understood and more specifically targeted.

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Transcriptional Differences between Normal and Glioma-Derived Glial Progenitor Cells Identify a Core Set of Dysregulated Genes

Abstract

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