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 J. Conway, Luis F. Parada, Yuan Zhu, Sean J. Morrison

Research output: Contribution to journalArticle

104 Scopus citations

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

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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., Conway, S. J., Parada, L. F., Zhu, Y., & 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