Submitted on January 20, 2006
Accepted on June 26, 2006
Tissue-Specific Stem Cells
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X-inactivation patterns of closely, but not distantly, related cells are highly correlated: little evidence for stem cell plasticity in normal females
Mark A. Vickers 1*,
Sarah J. Canning 1,
Wendy L. Craig 2,
Neil M. Masson 2,
Ian J. Wilson 3
1 Departments of Medicine and Therapeutics, Aberdeen University Medical School, Foresterhill, Aberdeen, United Kingdom
2 Department of Surgery, Aberdeen University Medical School, Foresterhill, Aberdeen, United Kingdom
3 Department of Mathematical Sciences, Aberdeen University Medical School, Foresterhill, Aberdeen, United Kingdom
* To whom correspondence should be addressed. E-mail: m.a.vickers{at}abdn.ac.uk.
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Abstract |
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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 (HUMARA) locus, in paired tissue samples from healthy individuals. Tissues sampled were stomach (18 informative females), duodenum (18), colon (10) with corresponding peripheral blood samples (33), and varicose veins (28) with corresponding T cells (26) and peripheral blood granulocytes (25). XIPs from samples thought to have common stem cell origins were highly correlated: multiple samples from single vein, r=0. 80 (n=24); T cells versus granulocytes, r=.67 (23); duodenum versus stomach, r=.63 (12). Blood cells and vessels are derived from a common hemangioblast, but XIP correlations were moderate or poor: vein versus T cells, r=0.42 (26); vein versus granulocytes, r=0.11 (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=0.23 (18); duodenum, r=0.21 (18); colon, r=0.034 (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.