Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA;
Blood. 2013 Sep 19;122(12):2047-51. doi: 10.1182/blood-2013-02-484444. Epub 2013 Aug 12.
Induced pluripotent stem cells (iPSCs) hold great promise for modeling human hematopoietic diseases. However, intrinsic variability in the capacities of different iPSC lines for hematopoietic development complicates comparative studies and is currently unexplained. We created and analyzed 3 separate iPSC clones from fibroblasts of 3 different normal individuals using a standardized approach that included excision of integrated reprogramming genes by Cre-Lox mediated recombination. Gene expression profiling and hematopoietic differentiation assays showed that independent lines from the same individual were generally more similar to one another than those from different individuals. However, one iPSC line (WT2.1) exhibited a distinctly different gene expression, proliferation rate, and hematopoietic developmental potential relative to all other iPSC lines. This "outlier" clone also acquired extensive copy number variations (CNVs) during reprogramming, which may be responsible for its divergent properties. Our data indicate how inherent and acquired genetic differences can influence iPSC properties, including hematopoietic potential.
诱导多能干细胞（iPSCs）在模拟人类造血疾病方面具有巨大的潜力。然而，不同 iPSC 系在造血发育能力方面的固有变异性使比较研究变得复杂，目前尚未得到解释。我们使用一种标准化的方法，从 3 个不同的正常人的成纤维细胞中创建和分析了 3 个独立的 iPSC 克隆，该方法包括通过 Cre-Lox 介导的重组切除整合的重编程基因。基因表达谱分析和造血分化实验表明，来自同一个体的独立系通常比来自不同个体的系彼此更相似。然而，一个 iPSC 系（WT2.1）的基因表达、增殖率和造血发育潜能与所有其他 iPSC 系明显不同。这个“异常”克隆在重编程过程中还获得了广泛的拷贝数变异（CNVs），这可能是其不同特性的原因。我们的数据表明内在和获得的遗传差异如何影响 iPSC 的特性，包括造血潜能。
