The Loss of Nf1 Transiently Promotes Self-Renewal but Not Tumorigenesis by Neural Crest Stem Cells

Nancy M. Joseph, Jack T. Mosher, Johanna Buchstaller, Paige Snider, Paul E. McKeever, Megan Lim, Simon Conway, Luis F. Parada, Yuan Zhu, Sean J. Morrison

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Neurofibromatosis is caused by the loss of neurofibromin (Nf1), leading to peripheral nervous system (PNS) tumors, including neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). A long-standing question has been whether these tumors arise from neural crest stem cells (NCSCs) or differentiated glia. Germline or conditional Nf1 deficiency caused a transient increase in NCSC frequency and self-renewal in most regions of the fetal PNS. However, Nf1-deficient NCSCs did not persist postnatally in regions of the PNS that developed tumors and could not form tumors upon transplantation into adult nerves. Adult P0a-Cre+Nf1fl/- mice developed neurofibromas, and Nf1+/-Ink4a/Arf-/- and Nf1/p53+/- mice developed MPNSTs, but NCSCs did not persist postnatally in affected locations in these mice. Tumors appeared to arise from differentiated glia, not NCSCs.

Original languageEnglish
Pages (from-to)129-140
Number of pages12
JournalCancer Cell
Volume13
Issue number2
DOIs
StatePublished - Feb 5 2008

Fingerprint

Neural Stem Cells
Neural Crest
Carcinogenesis
Peripheral Nervous System
Nervous System Neoplasms
Neurofibroma
Neurilemmoma
Neuroglia
Neurofibromin 1
Neoplasms
Neurofibromatoses
Transplantation

Keywords

  • CELLCYCLE
  • STEMCELL

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Joseph, N. M., Mosher, J. T., Buchstaller, J., Snider, P., McKeever, P. E., Lim, M., ... Morrison, S. J. (2008). The Loss of Nf1 Transiently Promotes Self-Renewal but Not Tumorigenesis by Neural Crest Stem Cells. Cancer Cell, 13(2), 129-140. https://doi.org/10.1016/j.ccr.2008.01.003

The Loss of Nf1 Transiently Promotes Self-Renewal but Not Tumorigenesis by Neural Crest Stem Cells. / Joseph, Nancy M.; Mosher, Jack T.; Buchstaller, Johanna; Snider, Paige; McKeever, Paul E.; Lim, Megan; Conway, Simon; Parada, Luis F.; Zhu, Yuan; Morrison, Sean J.

In: Cancer Cell, Vol. 13, No. 2, 05.02.2008, p. 129-140.

Research output: Contribution to journalArticle

Joseph, NM, Mosher, JT, Buchstaller, J, Snider, P, McKeever, PE, Lim, M, Conway, S, Parada, LF, Zhu, Y & Morrison, SJ 2008, 'The Loss of Nf1 Transiently Promotes Self-Renewal but Not Tumorigenesis by Neural Crest Stem Cells', Cancer Cell, vol. 13, no. 2, pp. 129-140. https://doi.org/10.1016/j.ccr.2008.01.003
Joseph NM, Mosher JT, Buchstaller J, Snider P, McKeever PE, Lim M et al. The Loss of Nf1 Transiently Promotes Self-Renewal but Not Tumorigenesis by Neural Crest Stem Cells. Cancer Cell. 2008 Feb 5;13(2):129-140. https://doi.org/10.1016/j.ccr.2008.01.003
Joseph, Nancy M. ; Mosher, Jack T. ; Buchstaller, Johanna ; Snider, Paige ; McKeever, Paul E. ; Lim, Megan ; Conway, Simon ; Parada, Luis F. ; Zhu, Yuan ; Morrison, Sean J. / The Loss of Nf1 Transiently Promotes Self-Renewal but Not Tumorigenesis by Neural Crest Stem Cells. In: Cancer Cell. 2008 ; Vol. 13, No. 2. pp. 129-140.
@article{76ee68ff069643afb024e91b152ed548,
title = "The Loss of Nf1 Transiently Promotes Self-Renewal but Not Tumorigenesis by Neural Crest Stem Cells",
abstract = "Neurofibromatosis is caused by the loss of neurofibromin (Nf1), leading to peripheral nervous system (PNS) tumors, including neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). A long-standing question has been whether these tumors arise from neural crest stem cells (NCSCs) or differentiated glia. Germline or conditional Nf1 deficiency caused a transient increase in NCSC frequency and self-renewal in most regions of the fetal PNS. However, Nf1-deficient NCSCs did not persist postnatally in regions of the PNS that developed tumors and could not form tumors upon transplantation into adult nerves. Adult P0a-Cre+Nf1fl/- mice developed neurofibromas, and Nf1+/-Ink4a/Arf-/- and Nf1/p53+/- mice developed MPNSTs, but NCSCs did not persist postnatally in affected locations in these mice. Tumors appeared to arise from differentiated glia, not NCSCs.",
keywords = "CELLCYCLE, STEMCELL",
author = "Joseph, {Nancy M.} and Mosher, {Jack T.} and Johanna Buchstaller and Paige Snider and McKeever, {Paul E.} and Megan Lim and Simon Conway and Parada, {Luis F.} and Yuan Zhu and Morrison, {Sean J.}",
year = "2008",
month = "2",
day = "5",
doi = "10.1016/j.ccr.2008.01.003",
language = "English",
volume = "13",
pages = "129--140",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - The Loss of Nf1 Transiently Promotes Self-Renewal but Not Tumorigenesis by Neural Crest Stem Cells

AU - Joseph, Nancy M.

AU - Mosher, Jack T.

AU - Buchstaller, Johanna

AU - Snider, Paige

AU - McKeever, Paul E.

AU - Lim, Megan

AU - Conway, Simon

AU - Parada, Luis F.

AU - Zhu, Yuan

AU - Morrison, Sean J.

PY - 2008/2/5

Y1 - 2008/2/5

N2 - Neurofibromatosis is caused by the loss of neurofibromin (Nf1), leading to peripheral nervous system (PNS) tumors, including neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). A long-standing question has been whether these tumors arise from neural crest stem cells (NCSCs) or differentiated glia. Germline or conditional Nf1 deficiency caused a transient increase in NCSC frequency and self-renewal in most regions of the fetal PNS. However, Nf1-deficient NCSCs did not persist postnatally in regions of the PNS that developed tumors and could not form tumors upon transplantation into adult nerves. Adult P0a-Cre+Nf1fl/- mice developed neurofibromas, and Nf1+/-Ink4a/Arf-/- and Nf1/p53+/- mice developed MPNSTs, but NCSCs did not persist postnatally in affected locations in these mice. Tumors appeared to arise from differentiated glia, not NCSCs.

AB - Neurofibromatosis is caused by the loss of neurofibromin (Nf1), leading to peripheral nervous system (PNS) tumors, including neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). A long-standing question has been whether these tumors arise from neural crest stem cells (NCSCs) or differentiated glia. Germline or conditional Nf1 deficiency caused a transient increase in NCSC frequency and self-renewal in most regions of the fetal PNS. However, Nf1-deficient NCSCs did not persist postnatally in regions of the PNS that developed tumors and could not form tumors upon transplantation into adult nerves. Adult P0a-Cre+Nf1fl/- mice developed neurofibromas, and Nf1+/-Ink4a/Arf-/- and Nf1/p53+/- mice developed MPNSTs, but NCSCs did not persist postnatally in affected locations in these mice. Tumors appeared to arise from differentiated glia, not NCSCs.

KW - CELLCYCLE

KW - STEMCELL

UR - http://www.scopus.com/inward/record.url?scp=38549102668&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38549102668&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2008.01.003

DO - 10.1016/j.ccr.2008.01.003

M3 - Article

VL - 13

SP - 129

EP - 140

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 2

ER -