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First published online August 25, 2005
Stem Cells Vol. 23 No. 10 November 2005, pp. 1468 -1478
doi:10.1634/stemcells.2004-0371; www.StemCells.com
© 2005 AlphaMed Press

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ORIGINAL ARTICLE-CHARACTERIZATION SERIES

X-Inactivation Status Varies in Human Embryonic Stem Cell Lines

Lisa M. Hoffmana, Lisa Hallb, Jennifer L. Battena, Holly Younga, Dheerja Pardasania, E. Edward Baetgec, Jeanne Lawrenceb, Melissa K. Carpentera

a Robarts Research Institute, Krembil Centre for Stem Cell Biology, London, Ontario, Canada;
b Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA;
c CyThera, Inc., San Diego, California, USA

Key Words. Human embryonic stem cells • Epigenesis • X-chromosome inactivation • Differentiation

Correspondence: Melissa K. Carpenter, Ph.D., CyThera, Inc., 3550 General Atomics Court, San Diego, California 92121, USA. Telephone: 858-455-2736; Fax: 858-455-3962; e-mail: mcarpenter{at}cytheraco.com

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.




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