Low-grade chromosomal mosaicism in human somatic and embryonic stem cell populations
Low-grade chromosomal mosaicism in human somatic and embryonic stem cell populations
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DOI：
10.1038/ncomms5227
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发表时间：
2014-06-01
影响因子：
16.6
通讯作者：
Spits, Claudia
中科院分区：
文献类型：
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作者：
Jacobs, Kurt;Mertzanidou, Afroditi;Spits, Claudia
目前关于人类细胞培养中染色体嵌合现象的知识主要是基于细胞遗传学带带方法。适用于单细胞的高分辨率全基因组分析方法的最新发展为遗传和细胞多样性提供了新的见解。在这里，我们使用单细胞阵列比较基因组杂交（aCGH）研究了92个个体人类细胞的遗传含量，包括成纤维细胞、羊膜细胞和胚胎干细胞（hESCs）。我们发现人类体细胞和胚胎干细胞培养显示出携带独特的巨酶规模染色体异常的细胞的显著部分，形成了传统细胞遗传学方法无法检测到的遗传镶嵌。通过aCGH对7个克隆hESC亚系的研究证实了这些发现。此外，荧光原位杂交显示，与体细胞相比，hESC中亚端粒区域的不稳定性增加。这种遗传异质性可能会影响实验结果，在hESC的情况下，影响其潜在的临床应用。
Current knowledge on chromosomal mosaicism in human cell cultures is mostly based on cytogenetic banding methods. The recent development of high-resolution full-genome analysis methods applicable to single cells is providing new insights into genetic and cellular diversity. Here we study the genetic content of 92 individual human cells, including fibroblasts, amniocytes and embryonic stem cells (hESCs), using single-cell array-based comparative genomic hybridization (aCGH). We find that human somatic and embryonic stem cell cultures show significant fractions of cells carrying unique megabase-scale chromosomal abnormalities, forming genetic mosaics that could not have been detected by conventional cytogenetic methods. These findings are confirmed by studying seven clonal hESC sub-lines by aCGH. Furthermore, fluorescent in situ hybridisation reveals an increased instability of the subtelomeric regions in hESC as compared to somatic cells. This genetic heterogeneity may have an impact on experimental results and, in the case of hESC, on their potential clinical use.