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Nf1的缺失会短暂促进神经嵴干细胞的自我更新，但不会促进其肿瘤发生。

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

作者信息

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

机构信息

Center for Stem Cell Biology, Howard Hughes Medical Institute, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA.

出版信息

Cancer Cell. 2008 Feb;13(2):129-40. doi: 10.1016/j.ccr.2008.01.003.

DOI:10.1016/j.ccr.2008.01.003
PMID:18242513
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2566828/
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+Nf1(fl/-) 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.

摘要

神经纤维瘤病由神经纤维瘤蛋白（Nf1）缺失引起，可导致外周神经系统（PNS）肿瘤，包括神经纤维瘤和恶性外周神经鞘瘤（MPNST）。长期以来的一个问题是，这些肿瘤是源自神经嵴干细胞（NCSC）还是分化的神经胶质细胞。胚系或条件性Nf1缺陷导致胎儿PNS大多数区域的NCSC频率和自我更新短暂增加。然而，Nf1缺陷的NCSC在出生后不会在PNS中发生肿瘤的区域持续存在，并且在移植到成年神经中时无法形成肿瘤。成年P0a-Cre+Nf1(fl/-)小鼠会发生神经纤维瘤，Nf1(+/-)Ink4a/Arf(-/-)和Nf1/p53(+/-)小鼠会发生MPNST，但NCSC在出生后不会在这些小鼠的受影响部位持续存在。肿瘤似乎源自分化的神经胶质细胞，而非NCSC。

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[1]
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[7]
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[8]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Induction of abnormal proliferation by nonmyelinating schwann cells triggers neurofibroma formation.

Cancer Cell. 2008-2

[2]
Identification and characterization of a novel Schwann and outflow tract endocardial cushion lineage-restricted periostin enhancer.

Dev Biol. 2007-7-15

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Neural crest-derived cells with stem cell features can be traced back to multiple lineages in the adult skin.

J Cell Biol. 2006-12-18

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Cancer Res. 2006-3-1

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Inactivation of NF1 in CNS causes increased glial progenitor proliferation and optic glioma formation.

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Nat Rev Neurosci. 2005-9

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Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma.

Cancer Cell. 2005-8

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Neurofibromatosis type 1 - a model for nervous system tumour formation?

Nat Rev Cancer. 2005-7

[9]
Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways.

Genes Dev. 2005-6-15

[10]
Neurofibromin regulates neural stem cell proliferation, survival, and astroglial differentiation in vitro and in vivo.

J Neurosci. 2005-6-8

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