cancer cell 文章：自我更新能力并不能完全等价于肿瘤生长能力

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Self-Renewal Does Not Predict Tumor Growth Potential in Mouse Models of High-Grade GliomaSummaryLoading...7 f2 T/ ~, B4 n  c
( _  L. M; F. G
Cancer Cell, Volume 21, Issue 1, 11-24, 17 January 2012: b' z- }) y/ y; q0 ?) s
Copyright  2012 Elsevier Inc. All rights reserved.9 I; H) }1 R3 W! p" f
10.1016/j.ccr.2011.11.0251 d& t( b  l! ~
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Lindy E. Barrett, Zvi Granot, Courtney Coker, Antonio Iavarone, Dolores Hambardzumyan, Eric C. Holland, Hyung-song Nam, Robert BenezraSee AffiliationsHint: Rollover Authors and Affiliations Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA Institute for Cancer Genetics, Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, OH 44195, USA Corresponding author Present address: Howard Hughes Medical Institute and Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA4 T3 A# d# o/ O7 p4 I

0 @# |- J1 z0 fHighlights
6 k" t: L' a! A  I1 }•Id1 identifies self-renewing glioma cells 1 c8 H) b4 u# A+ `& j
•Self-renewal is not required for glioma growth in PDGF- and KRAS-driven tumors - \3 r3 v; z0 \7 \( ?; F/ \3 A
•Purified progenitor cells efficiently transplant gliomas
! |' e; }$ @2 f0 @1 F•Id1 high self-renewing cells can generate aggressive progenitors
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Within high-grade gliomas, the precise identities and functional roles of stem-like cells remain unclear. In the normal neurogenic niche, ID (Inhibitor of DNA-binding) genes maintain self-renewal and multipotency of adult neural stem cells. Using PDGF- and KRAS-driven murine models of gliomagenesis, we show that high Id1 expression (Id1high) identifies tumor cells with high self-renewal capacity, while low Id1 expression (Id1low) identifies tumor cells with proliferative potential but limited self-renewal capacity. Surprisingly, Id1low cells generate tumors more rapidly and with higher penetrance than Id1high cells. Further, eliminating tumor cell self-renewal through deletion of Id1 has modest effects on animal survival, while knockdown of Olig2 within Id1low cells has a significant survival benefit, underscoring the importance of non-self-renewing lineages in disease progression.$ _0 h, f, R. l" U( p" H% _" o

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3 g- Z/ @, z+ A: y/ A: `- x请教一个幼稚的问题：什么能力算是是自我更新能力？Oct-4, Sox2,Nanog 这些多能性基因对于维持胚胎干细胞的自我更新能力很重要，那对于它们的增殖能力呢？另外，什么样的基因被称为多能性基因呢？肿瘤干细胞与胚胎干细胞有共同的多能性基因么？

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1.什么能力算是是自我更新能力？
: `; T1 Y7 b/ m/ w自我更新能力是相对于干细胞而言的，简单地说自我更新就是一个干细胞在分裂时所产生的子细胞中至少存在一个细胞具备有母细胞所具备的干细胞性质，相当于再生过程。$ [7 [, T: z; n& J
2. Oct-4, Sox2,Nanog 这些多能性基因对于维持胚胎干细胞的自我更新能力很重要，那对于它们的增殖能力呢？1 E) n. o: m* ?( N& t) t: `. s
关于增殖问题，如果都是存在干细胞横向分裂（相对于干细胞纵向分化而言）过程中，那么增殖能力就相当于自我更新能力。( A  v/ F: f6 t- n5 B
3. 另外，什么样的基因被称为多能性基因呢？
4 v  Q5 o- C* q4 T' }3 x2 t& ^多能性基因就是指对于维持干细胞多分化潜能具有重要作用的基因。
1 X- {8 O+ s$ ^8 }# W1 J$ U4. 肿瘤干细胞与胚胎干细胞有共同的多能性基因么？  Y( R) w4 _: C
有，oct4, c-myc,等等，当然很多蛋白与正常干细胞表达的蛋白可能在蛋白表面修饰上会有些区别。 还有一些干细胞共用的信号通路。例如：Notch, Wnt等等
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