7月6日，Cell Stem Cell杂志报道，来源于男性和女性的人类诱导多能干细胞，在表观遗传稳定性和癌基因的表达方面均有较大的差异。
虽然人类诱导多能干细胞（hiPSCs）在再生医学中具有巨大潜力，他们的表观遗传变异性表明，有些hiPSCs细胞系可能不适合人类治疗。目前对hiPSCs进行质量评估的基准很有限。
本研究表明，X染色体失活标记可以用来将表观遗传学上独特的hiPSCs和表型上独特的hiPSCs区分开来。XIST(X-inactive specific transcript)是一个X染色体上的胎盘哺乳动物的X染色体失活过程中发挥主要效应的RNA基因。Xist表达的缺失与X-连锁癌基因的表达上调、细胞在体外加速增长，在体内较差的分化密切相关。
在X染色体失活潜力的差异可导致女性hiPSC细胞系在表观遗传学上的差异，而男性hiPSC细胞系一般彼此相似，并且不过度表达癌基因。
生理水平的氧气含量和组蛋白去乙酰化酶（HDAC）抑制剂均不能促进女性hiPSC细胞系的培养。
据此，研究者得出这样的结论：在培养条件下，女性hiPSCs的表观遗传稳定性比男性的较差；Xist的丢失可能导致质量不理想的干细胞系。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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Molecular Signatures of Human Induced Pluripotent Stem Cells Highlight Sex Differences and Cancer Genes
Montserrat C. Anguera, Ruslan Sadreyev, Zhaoqing Zhang, Attila Szanto, Bernhard Payer, Steven D. Sheridan, Showming Kwok, Stephen J. Haggarty, Mriganka Sur, Jason Alvarez, Alexander Gimelbrant, Maisam Mitalipova, James E. Kirby, Jeannie T. Lee
Although human induced pluripotent stem cells (hiPSCs) have enormous potential in regenerative medicine, their epigenetic variability suggests that some lines may not be suitable for human therapy. There are currently few benchmarks for assessing quality. Here we show that X-inactivation markers can be used to separate hiPSC lines into distinct epigenetic classes and that the classes are phenotypically distinct. Loss of XIST expression is strongly correlated with upregulation of X-linked oncogenes, accelerated growth rate in vitro, and poorer differentiation in vivo. Whereas differences in X-inactivation potential result in epigenetic variability of female hiPSC lines, male hiPSC lines generally resemble each other and do not overexpress the oncogenes. Neither physiological oxygen levels nor HDAC inhibitors offer advantages to culturing female hiPSC lines. We conclude that female hiPSCs may be epigenetically less stable in culture and caution that loss of XIST may result in qualitatively less desirable stem cell lines.
