X-Inactivation Varies in hESC Lines

¹ Robarts Research Institute, London, Ontario, Canada
² Massachusetts Medical School, Worcester, Massachusetts
³ CyThera, Inc, San Diego, California

^* To whom correspondence should be addressed. E-mail: mcarpenter{at}cytheraco.com.

	Abstract

Human embryonic stem cells (hESCs) derived from human blastocysts have an apparently unlimited proliferative capacity, and can differentiate into ectoderm, mesoderm and endoderm. As such, hESC lines have enormous potential for use in cell replacement therapies. It must first be demonstrated, however, that hESCs maintain a stable karyotype and phenotype, and that gene expression is appropriately regulated. To date, different hESC lines exhibit similar patterns of expression of markers associated with pluripotent cells. However, the evaluation of epigenetic status of hESC lines has only recently been initiated. One example of epigenetic gene regulation is dosage compensation of the X chromosome in mammalian females. This is achieved through an epigenetic event referred to as X-chromosome inactivation (XCI), an event initiated upon cellular differentiation. We provide the first evidence that undifferentiated hESC lines exhibit different patterns of XCI.

This article has been cited by other articles:

				X. Sun, X. Long, Y. Yin, Y. Jiang, X. Chen, W. Liu, W. Zhang, H. Du, S. Li, Y. Zheng, et al. Similar biological characteristics of human embryonic stem cell lines with normal and abnormal karyotypes Hum. Reprod., October 1, 2008; 23(10): 2185 - 2193. [Abstract] [Full Text] [PDF]

				Y. Shen, Y. Matsuno, S. D. Fouse, N. Rao, S. Root, R. Xu, M. Pellegrini, A. D. Riggs, and G. Fan X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations PNAS, March 25, 2008; 105(12): 4709 - 4714. [Abstract] [Full Text] [PDF]

				S. S. Silva, R. K. Rowntree, S. Mekhoubad, and J. T. Lee X-chromosome inactivation and epigenetic fluidity in human embryonic stem cells PNAS, March 25, 2008; 105(12): 4820 - 4825. [Abstract] [Full Text] [PDF]

				C. S. Navara, J. D. Mich-Basso, C. J. Redinger, A. Ben-Yehudah, E. Jacoby, E. Kovkarova-Naumovski, M. Sukhwani, K. Orwig, N. Kaminski, C. A. Castro, et al. Pedigreed Primate Embryonic Stem Cells Express Homogeneous Familial Gene Profiles Stem Cells, November 1, 2007; 25(11): 2695 - 2704. [Abstract] [Full Text] [PDF]

				J. C. Chow, L. L. Hall, S. E. L. Baldry, N. P. Thorogood, J. B. Lawrence, and C. J. Brown Inducible XIST-dependent X-chromosome inactivation in human somatic cells is reversible PNAS, June 12, 2007; 104(24): 10104 - 10109. [Abstract] [Full Text] [PDF]

				C. Allegrucci and L.E. Young Differences between human embryonic stem cell lines Hum. Reprod. Update, March 1, 2007; 13(2): 103 - 120. [Abstract] [Full Text] [PDF]

				A. Hellman and A. Chess Gene Body-Specific Methylation on the Active X Chromosome Science, February 23, 2007; 315(5815): 1141 - 1143. [Abstract] [Full Text] [PDF]

				M. A. Vickers, S. J. Canning, W. L. Craig, N. M. Masson, and I. J. Wilson X Inactivation Patterns of Closely, but Not Distantly, Related Cells Are Highly Correlated: Little Evidence for Stem Cell Plasticity in Normal Females Stem Cells, November 1, 2006; 24(11): 2398 - 2405. [Abstract] [Full Text] [PDF]

				M. S. Rao One Successful Series Begets Another Stem Cells, October 1, 2006; 24(10): 2160 - 2161. [Full Text] [PDF]

				M. Bibikova, E. Chudin, B. Wu, L. Zhou, E. W. Garcia, Y. Liu, S. Shin, T. W. Plaia, J. M. Auerbach, D. E. Arking, et al. Human embryonic stem cells have a unique epigenetic signature Genome Res., September 1, 2006; 16(9): 1075 - 1083. [Abstract] [Full Text] [PDF]