7月6日，Cell Stem Cell雜志報(bào)道,，來源于男性和女性的人類誘導(dǎo)多能干細(xì)胞,，在表觀遺傳穩(wěn)定性和癌基因的表達(dá)方面均有較大的差異,。
雖然人類誘導(dǎo)多能干細(xì)胞（hiPSCs）在再生醫(yī)學(xué)中具有巨大潛力,，他們的表觀遺傳變異性表明,，有些hiPSCs細(xì)胞系可能不適合人類治療。目前對hiPSCs進(jìn)行質(zhì)量評估的基準(zhǔn)很有限,。
本研究表明,，X染色體失活標(biāo)記可以用來將表觀遺傳學(xué)上獨(dú)特的hiPSCs和表型上獨(dú)特的hiPSCs區(qū)分開來。XIST(X-inactive specific transcript)是一個(gè)X染色體上的胎盤哺乳動(dòng)物的X染色體失活過程中發(fā)揮主要效應(yīng)的RNA基因,。Xist表達(dá)的缺失與X-連鎖癌基因的表達(dá)上調(diào),、細(xì)胞在體外加速增長，在體內(nèi)較差的分化密切相關(guān),。
在X染色體失活潛力的差異可導(dǎo)致女性hiPSC細(xì)胞系在表觀遺傳學(xué)上的差異,，而男性hiPSC細(xì)胞系一般彼此相似，并且不過度表達(dá)癌基因,。
生理水平的氧氣含量和組蛋白去乙?；福℉DAC）抑制劑均不能促進(jìn)女性hiPSC細(xì)胞系的培養(yǎng)。
據(jù)此,，研究者得出這樣的結(jié)論：在培養(yǎng)條件下,，女性hiPSCs的表觀遺傳穩(wěn)定性比男性的較差；Xist的丟失可能導(dǎo)致質(zhì)量不理想的干細(xì)胞系,。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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PMID:
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.
