Characterization of human embryonic stem cells with features of neoplastic progression
Characterization of human embryonic stem cells with features of neoplastic progression
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DOI：
10.1038/nbt.1516
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发表时间：
2009-01-01
影响因子：
46.9
通讯作者：
Bhatia, Mickie
中科院分区：
文献类型：
--
作者：
Werbowetski-Ogilvie, Tamra E.;Bosse, Marc;Bhatia, Mickie
培养的人类胚胎干细胞（hES）可以获得遗传和表观遗传的变化，使他们容易转化。由于具有癌细胞特征的hES细胞与正常hES细胞具有共同的特性，例如自我更新、畸胎瘤形成和多能性标记物的表达，因此它们可能被误解为具有增强的“干细胞性”的上级hES细胞。我们表征了两种变体hES细胞系（v-hESC-1和v-hESC-2），其以高水平表达多能性标志物，并且通过标准细胞遗传学测量不具有染色体异常。我们发现，这两个线具有肿瘤进展的一些功能，包括高增殖能力，生长因子的独立性，肿瘤起始细胞的频率增加9至20倍，生态位的独立性和异常的谱系规范，虽然它们不是恶性的。阵列比较基因组杂交显示v-hESC-1在20q11.1-11.2扩增，v-hESC-2在5 q34 a-5 q34 b; 5 q3缺失，12号染色体嵌合获得。这些结果强调需要功能表征，以区分部分转化和正常的hES细胞。(C)2009 Nature America，Inc. All rights reserved.
Cultured human embryonic stem (hES) cells can acquire genetic and epigenetic changes that make them vulnerable to transformation. As hES cells with cancer-cell characteristics share properties with normal hES cells, such as self-renewal, teratoma formation and the expression of pluripotency markers, they may be misconstrued as superior hES cells with enhanced 'stemness'. We characterize two variant hES cell lines (v-hESC-1 and v-hESC-2) that express pluripotency markers at high levels and do not harbor chromosomal abnormalities by standard cytogenetic measures. We show that the two lines possess some features of neoplastic progression, including a high proliferative capacity, growth-factor independence, a 9- to 20-fold increase in frequency of tumor-initiating cells, niche independence and aberrant lineage specification, although they are not malignant. Array comparative genomic hybridization reveals an amplification at 20q11.1-11.2 in v-hESC-1 and a deletion at 5q34a-5q34b; 5q3 and a mosaic gain of chromosome 12 in v-hESC-2. These results emphasize the need for functional characterization to distinguish partially transformed and normal hES cells. (C) 2009 Nature America, Inc. All rights reserved.