The probable cell of origin of NF1- and PDGF-Driven glioblastomas

Dolores Hambardzumyan, Yu Kang Cheng, Hiroshi Haeno, Eric C. Holland, Franziska Michor

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Primary glioblastomas are subdivided into several molecular subtypes. There is an ongoing debate over the cell of origin for these tumor types where some suggest a progenitor while others argue for a stem cell origin. Even within the same molecular subgroup, and using lineage tracing in mouse models, different groups have reached different conclusions. We addressed this problem from a combined mathematical modeling and experimental standpoint. We designed a novel mathematical framework to identify the most likely cells of origin of two glioma subtypes. Our mathematical model of the unperturbed in vivo system predicts that if a genetic event contributing to tumor initiation imparts symmetric self-renewing cell division (such as PDGF overexpression), then the cell of origin is a transit amplifier. Otherwise, the initiating mutations arise in stem cells. The mathematical framework was validated with the RCAS/tv-a system of somatic gene transfer in mice. We demonstrated that PDGF-induced gliomas can be derived from GFAP-expressing cells of the subventricular zone or the cortex (reactive astrocytes), thus validating the predictions of our mathematical model. This interdisciplinary approach allowed us to determine the likelihood that individual cell types serve as the cells of origin of gliomas in an unperturbed system.

Original languageEnglish
Article numbere24454
JournalPloS one
Volume6
Issue number9
DOIs
Publication statusPublished - Sep 9 2011

Fingerprint

Glioblastoma
Stem cells
Tumors
Mathematical models
Gene transfer
Glioma
mathematical models
Cells
cells
stem cells
Theoretical Models
Stem Cells
neoplasms
Lateral Ventricles
astrocytes
gene transfer
Astrocytes
Cell Division
cell division
Neoplasms

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hambardzumyan, D., Cheng, Y. K., Haeno, H., Holland, E. C., & Michor, F. (2011). The probable cell of origin of NF1- and PDGF-Driven glioblastomas. PloS one, 6(9), [e24454]. https://doi.org/10.1371/journal.pone.0024454

The probable cell of origin of NF1- and PDGF-Driven glioblastomas. / Hambardzumyan, Dolores; Cheng, Yu Kang; Haeno, Hiroshi; Holland, Eric C.; Michor, Franziska.

In: PloS one, Vol. 6, No. 9, e24454, 09.09.2011.

Research output: Contribution to journalArticle

Hambardzumyan, D, Cheng, YK, Haeno, H, Holland, EC & Michor, F 2011, 'The probable cell of origin of NF1- and PDGF-Driven glioblastomas', PloS one, vol. 6, no. 9, e24454. https://doi.org/10.1371/journal.pone.0024454
Hambardzumyan D, Cheng YK, Haeno H, Holland EC, Michor F. The probable cell of origin of NF1- and PDGF-Driven glioblastomas. PloS one. 2011 Sep 9;6(9). e24454. https://doi.org/10.1371/journal.pone.0024454
Hambardzumyan, Dolores ; Cheng, Yu Kang ; Haeno, Hiroshi ; Holland, Eric C. ; Michor, Franziska. / The probable cell of origin of NF1- and PDGF-Driven glioblastomas. In: PloS one. 2011 ; Vol. 6, No. 9.
@article{5e6fa0c1101641f493d32a6af8278b4b,
title = "The probable cell of origin of NF1- and PDGF-Driven glioblastomas",
abstract = "Primary glioblastomas are subdivided into several molecular subtypes. There is an ongoing debate over the cell of origin for these tumor types where some suggest a progenitor while others argue for a stem cell origin. Even within the same molecular subgroup, and using lineage tracing in mouse models, different groups have reached different conclusions. We addressed this problem from a combined mathematical modeling and experimental standpoint. We designed a novel mathematical framework to identify the most likely cells of origin of two glioma subtypes. Our mathematical model of the unperturbed in vivo system predicts that if a genetic event contributing to tumor initiation imparts symmetric self-renewing cell division (such as PDGF overexpression), then the cell of origin is a transit amplifier. Otherwise, the initiating mutations arise in stem cells. The mathematical framework was validated with the RCAS/tv-a system of somatic gene transfer in mice. We demonstrated that PDGF-induced gliomas can be derived from GFAP-expressing cells of the subventricular zone or the cortex (reactive astrocytes), thus validating the predictions of our mathematical model. This interdisciplinary approach allowed us to determine the likelihood that individual cell types serve as the cells of origin of gliomas in an unperturbed system.",
author = "Dolores Hambardzumyan and Cheng, {Yu Kang} and Hiroshi Haeno and Holland, {Eric C.} and Franziska Michor",
year = "2011",
month = "9",
day = "9",
doi = "10.1371/journal.pone.0024454",
language = "English",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - The probable cell of origin of NF1- and PDGF-Driven glioblastomas

AU - Hambardzumyan, Dolores

AU - Cheng, Yu Kang

AU - Haeno, Hiroshi

AU - Holland, Eric C.

AU - Michor, Franziska

PY - 2011/9/9

Y1 - 2011/9/9

N2 - Primary glioblastomas are subdivided into several molecular subtypes. There is an ongoing debate over the cell of origin for these tumor types where some suggest a progenitor while others argue for a stem cell origin. Even within the same molecular subgroup, and using lineage tracing in mouse models, different groups have reached different conclusions. We addressed this problem from a combined mathematical modeling and experimental standpoint. We designed a novel mathematical framework to identify the most likely cells of origin of two glioma subtypes. Our mathematical model of the unperturbed in vivo system predicts that if a genetic event contributing to tumor initiation imparts symmetric self-renewing cell division (such as PDGF overexpression), then the cell of origin is a transit amplifier. Otherwise, the initiating mutations arise in stem cells. The mathematical framework was validated with the RCAS/tv-a system of somatic gene transfer in mice. We demonstrated that PDGF-induced gliomas can be derived from GFAP-expressing cells of the subventricular zone or the cortex (reactive astrocytes), thus validating the predictions of our mathematical model. This interdisciplinary approach allowed us to determine the likelihood that individual cell types serve as the cells of origin of gliomas in an unperturbed system.

AB - Primary glioblastomas are subdivided into several molecular subtypes. There is an ongoing debate over the cell of origin for these tumor types where some suggest a progenitor while others argue for a stem cell origin. Even within the same molecular subgroup, and using lineage tracing in mouse models, different groups have reached different conclusions. We addressed this problem from a combined mathematical modeling and experimental standpoint. We designed a novel mathematical framework to identify the most likely cells of origin of two glioma subtypes. Our mathematical model of the unperturbed in vivo system predicts that if a genetic event contributing to tumor initiation imparts symmetric self-renewing cell division (such as PDGF overexpression), then the cell of origin is a transit amplifier. Otherwise, the initiating mutations arise in stem cells. The mathematical framework was validated with the RCAS/tv-a system of somatic gene transfer in mice. We demonstrated that PDGF-induced gliomas can be derived from GFAP-expressing cells of the subventricular zone or the cortex (reactive astrocytes), thus validating the predictions of our mathematical model. This interdisciplinary approach allowed us to determine the likelihood that individual cell types serve as the cells of origin of gliomas in an unperturbed system.

UR - http://www.scopus.com/inward/record.url?scp=80052559874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052559874&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0024454

DO - 10.1371/journal.pone.0024454

M3 - Article

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e24454

ER -