@article{f1c9f10f9f274903b39ecb4fd8771b17,
title = "Derivation conditions impact x-inactivation status in female human induced pluripotent stem cells",
abstract = "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 Xas 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.",
author = "Kiichiro Tomoda and Kazutoshi Takahashi and Karen Leung and Aki Okada and Megumi Narita and Yamada, \{N. Alice\} and Eilertson, \{Kirsten E.\} and Peter Tsang and Shiro Baba and White, \{Mark P.\} and Salma Sami and Deepak Srivastava and Conklin, \{Bruce R.\} and Barbara Panning and Shinya Yamanaka",
note = "Funding Information: We thank members of the Yamanaka laboratory for useful discussions, Tim Rand for plotting the results of bisulfite sequencing and X/A ratios, Kenta Nakamura for hiPSC differentiation and useful discussions, Laura Mitic for maintaining the confocal microscope, Lei Lue for the endothelial cell differentiation, Michiyo Koyanagi for microarray analyses, Mari Ohnuki for discussion of neural differentiation, Gary Howard and Anna Lisa Lucido for editorial review, Karena Essex for administrative supports, Stem Cell Core for providing stem cell culture services, and Bioinformatics Core for conducting the statistic analyses. We also would like to thank Kathrin Plath and Sanjeet Patel for providing their hiPSC lines. K.T. is a scholar of the California Institute for Regenerative Medicine (CIRM). K.L. is supported by an NIH fellowship (F32 GM099389-01A1). B.P. is funded by NIH R01 GM088506. This work was supported in part by grants from the Leading Project of MEXT (Japan, to S.Y.), the Funding Program for World-Leading Innovative R\&D on Science and Technology (FIRST Program) of the JSPS (Japan, to S.Y.), Grants-in-Aid for Scientific Research of the JSPS and MEXT (Japan, to S.Y.), and the Program for Promotion of Fundamental Studies in Health Sciences of NIBIO (Japan, to S.Y.). These studies were also made possible by funding from the Gladstone Institutes, the L.K. Whittier Foundation, NHLBI/NIH (U01-HL100406, U01-HL098179), and the CIRM. The Gladstone Institutes received support from a National Center for Research Resources Grant RR18928-01. S.Y. is a member without salary of the Scientific Advisory Board of iPierian, iPS Academia Japan, and Megakaryon Corporation; D.S. is a member of the Scientific Advisory Board of iPierian, Inc. and RegeneRx Pharmaceuticals; B.R.C. is a member of the Scientific Advisory Board of iPierian, Inc.; and N.A.Y. and P.T. are employees of Agilent Technologies, Inc. ",
year = "2012",
month = jul,
day = "6",
doi = "10.1016/j.stem.2012.05.019",
language = "English (US)",
volume = "11",
pages = "91--99",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "1",
}