Derivation Conditions Impact X-Inactivation Status in Female Human Induced Pluripotent Stem Cells

作者：Tomoda Kiichiro; Takahashi Kazutoshi; Leung Karen; Okada Aki; Narita Megumi; Yamada N Alice; Eilertson Kirsten E; Tsang Peter; Baba Shiro; White Mark P; Sarni Salma; Srivastava Deepak; Conklin Bruce R; Panning Barbara^*; Yamanaka Shinya

来源：Cell Stem Cell, 2012, 11(1): 91-99.

DOI：10.1016/j.stem.2012.05.019

Female human induced pluripotent stem cell (hiPSC) lines exhibit variability in X-inactivation status. The majority of hiPSC lines maintain one transcriptionally active X (Xa) and one inactive X (Xi) chromosome from donor cells. However, at low frequency, hiPSC lines with two)(as are produced, suggesting that epigenetic alterations of the Xi occur sporadically during reprogramming. We show here that X-inactivation status in female hiPSC lines depends on derivation conditions. hiPSC Lines generated by the Kyoto method (retroviral or episomal reprogramming), which uses leukemia inhibitory factor (LIF)-expressing SNL feeders, frequently had two Xas. Early passage Xa/Xi hiPSC lines generated on non-SNL feeders were converted into Xa/Xa hiPSC lines after several passages on SNL feeders, and supplementation with recombinant LIF caused reactivation of some of X-linked genes. Thus, feeders are a significant factor affecting X-inactivation status. The efficient production of Xa/Xa hiPSC lines provides unprecedented opportunities to understand human X-reactivation and -inactivation.

• 出版日期2012-7-6