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First published online July 6, 2006
Stem Cells Vol. 24 No. 11 November 2006, pp. 2398 -2405
doi:10.1634/stemcells.2006-0043; www.StemCells.com
© 2006 AlphaMed Press

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TISSUE-SPECIFIC STEM CELLS

X Inactivation Patterns of Closely, but Not Distantly, Related Cells Are Highly Correlated: Little Evidence for Stem Cell Plasticity in Normal Females

Mark A. Vickersa, Sarah J. Canninga, Wendy L. Craigb, Neil M. Massonb, Ian J. Wilsonc

Departments of aMedicine and Therapeutics,
bSurgery, and
cMathematical Sciences, Aberdeen University Medical School, Foresterhill, Aberdeen, United Kingdom

Key Words. Biomathematical modeling • T cells • Stem cell plasticity • Somatic stem cells • Pluripotent stem cells • Multipotential differentiation • Granulocytes

Correspondence: Mark A. Vickers, B.M, B.Ch., D.M., F.R.C.Path., Department of Medicine and Therapeutics, Polwarth Building, Foresterhill, Aberdeen AB25 22D, United Kingdom. Telephone: 01224-553026; Fax: 01224-554761; e-mail: m.a.vickers{at}abdn.ac.uk

Received January 20, 2006; accepted for publication June 26, 2006.
First published online in STEM CELLS EXPRESS   July 6, 2006.



The early, random nature of X inactivation should cause related cells to have similar, but distinctive, active X chromosomes. We assessed the frequency of stem cell plasticity using X inactivation proportions (XIPs), determined at the human androgen receptor locus, in paired tissue samples from healthy individuals. Tissues sampled were stomach (n = 18 informative females), duodenum (n = 18), colon (n = 10) with corresponding peripheral blood samples (n = 33), and varicose veins (n = 28) with corresponding T cells (n = 26) and peripheral blood granulocytes (n = 25). XIPs from samples thought to have common stem cell origins were highly correlated: multiple samples from single vein, r = .80 (n = 24); T cells versus granulocytes, r = .67 (n = 23); duodenum versus stomach, r = .63 (n = 12). Blood cells and vessels are derived from a common hemangioblast, but XIP correlations were moderate or poor: vein versus T cells, r = .42 (n = 26); vein versus granulocytes, r = .11 (n = 25). X inactivation is believed to be a late process in gut, especially hind-gut, with corresponding independence from blood precursors. Correlations with blood cells were low: stomach, r = .23 (18); duodenum, r = .21 (18); colon, r = .034 (10). Any crossover of stem cells between different organs during adult life should increase correlations with age; no such increase was seen. This study confirms that XIPs can be used to track stem cell populations, provides a theoretical basis for the power of such studies, and indicates that hemopoietic stem cell plasticity is, at most, uncommon in normal humans.







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