[PDF][PDF] The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells

NM Joseph, JT Mosher, J Buchstaller, P Snider… - Cancer cell, 2008 - cell.com
NM Joseph, JT Mosher, J Buchstaller, P Snider, PE McKeever, M Lim, SJ Conway
Cancer cell, 2008cell.com
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 …
Summary
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.
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