我们科室之前发现了核型变异的人胚胎干细胞株

f5_105

我们科室之前发现了核型变异的人胚胎干细胞株，并将之与正常人胚胎干细胞和畸胎癌细胞进行了比较，发现其表达谱介于后两者之间，提示人胚胎干细胞的遗传变异很有可能是肿瘤的来源方式之一。有兴趣的同志可以参阅文献《Tumor Progression of Culture-Adapted Human Embryonic Stem Cells During Long-Term Culture》5 f1 q. ]. D6 v0 |
个人认为，肿瘤干细胞的来源不会是单一的，各种因素的影响都可能诱发肿瘤干细胞的发生，从原始细胞如胚胎干细胞直接来源或者由体细胞重新获得干性+肿瘤特性都是有可能的。作为胚胎干细胞的研究者，我最关心的是如何找到比核型分析有效的标记区分原始肿瘤干细胞和正常的胚胎干细胞，防止胚胎干细胞肿瘤化，为胚胎干细胞的临床应用铺平道路。

longer

Genes Chromosomes Cancer. 2008 Aug;47(8):665-79.
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Tumor progression of culture-adapted human embryonic stem cells during long-term culture.3 |, i2 p! K2 h
Yang S, Lin G, Tan YQ, Zhou D, Deng LY, Cheng DH, Luo SW, Liu TC, Zhou XY, Sun Z, Xiang Y, Chen TJ, Wen JF, Lu GX.: j* s  e" p& }: ^6 L. S! w
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National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction & Stem Cell Engineering, Central South University, Changsha, China.
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Abstract
+ P8 O3 i- a9 p! mHuman embryonic stem cells (hESCs) during long-term culture acquire chromosomal changes similar to those occurring in tumorigenesis. This was raised concerns about the progression from hESCs to malignant cells. This study aimed to investigate the changes in chromosomes, cell phenotype, and genes in culture-adapted hESCs to ascertain whether tumorigenic transformation occurred. By cytogenetic analysis we found progressive karyotypic changes from simple to complex in chHES-3, one of the hESC lines established in our laboratory, during a long-term suboptimal culture. We further compared chHES-3 cells at different karyotypic stages in cell surface markers, in vivo differentiation, cell cycle, apoptosis, and gene expression profiles. We found that the karyotypically aberrant chHES-3 had higher S-phase fraction in cell cycle distributions and antiapoptosis ability. In vivo differentiation of karyotypically normal chHES-3 resulted in relatively mature teratoma, whereas karyotypically aberrant chHES-3 formed immature teratoma (grade III), in which more primary neural epithelium was revealed by pathological analysis. The microarray analysis and real-time PCR results showed that some oncogenes were upregulated in karyotypically aberrant chHES-3 cells, whereas the genes related to differentiation were downregulated, and that Wnt signal pathway was activated. In conclusion, chHES-3 cells underwent deregulation of self-renewal and dysfunction of related genes in long-term culture adaptation, leading to malignant transformation.
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6 s: y/ G% ]: t(c) 2008 Wiley-Liss, Inc.6 g" x( L8 y& B4 v
PMID: 18470900 [PubMed - indexed for MEDLINE]1 L6 j% X0 T# |" |3 [2 Q9 U- D; T

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Publication Types, MeSH TermsPublication Types: Research Support, Non-U.S. Gov'tMeSH Terms:Cell Culture TechniquesCell Transformation, Neoplastic*/geneticsCell Transformation, Neoplastic*/pathologyCells, CulturedCytogenetic AnalysisEmbryonic Stem Cells/pathology*Gene Expression ProfilingHumansNeoplastic ProcessesS Phase/genetics
( Y6 @  ^) t3 ^, j7 RLinkOut - more resourcesFull Text Sources:6 W/ Y$ y! _( t  W+ i8 V6 N
John Wiley & Sons, Inc.3 {' n! A5 y. J/ P/ u& J7 M/ V: d* f
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OhioLINK Electronic Journal Center8 v7 [" R) @# L1 r7 a' g
Swets Information Services
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dnarna

到目前为止，这个细胞株总共传了多少代（从发现变异开始），其细胞形态特征等是否有改变？

sunsong7

老狼认为这个发现很有意思。% Q0 j$ k/ a8 H2 Q! }7 A
从已有报道可以得到这样的结论：成体细胞在体内可以去分化为全能干细胞（内源性iPS或ES？），全能干细胞在成体内（非胚胎性微环境中）可以转化为肿瘤。或者至少说：成体细胞通过内源性胚胎干细胞转化为肿瘤这条路线是通的。
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9 Z" ]! i0 \* r  X/ S: r扩展阅读：癌细胞的发生可能是一种“返祖”现象？http://www.stemcell8.cn/thread-32073-1-1.html
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f5_105

回复 dnarna 的帖子* B$ V( D4 A3 y+ q
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传了200多代，在克隆形态和ES多能性标记方面与普通的ES细胞株没有明显差异。核型的变异是从简单到复杂的，文章中有描述。

dnarna

大概看下文章，做得很细致很漂亮。% f( X5 a' o. e7 E
有些奇怪的是：
; M8 Z: Y. P. R/ U1 q1，为什么RT中COMP HES-3 cells的OCT4明显上调，而在Identical morphology of colonies 图中显色极少---蛋白表达水平下调？（在 immunohistological analyses of tumors. (A–C) Teratoma 却很明显）。
5 S& s0 B3 N2 A) s# S+ c2，SOX2的RT结果似乎明显分子量大小有变（不像电泳跑偏）。8 Y0 \/ A) L" f7 X2 K( R1 V! s
3，NANOG的组化没做？/ T1 E- N+ b) ?6 M: V. }
4，telomerase activity 分析中 HES-3 cells细胞尤其是COMP HES-3 cells的带型有明显不同之处，是否有合适的解释？
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×这个细胞系应是个好材料，现在还有人用它继续研究吗？' U4 ^6 Z: ~  d8 L# Q4 w