X inactivation patterns of closely, but not distantly, related cells are highly correlated: little evidence for stem cell plasticity in normal females.
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.
Vickers
Mark A
MA
Department of Medicine and Therapeutics, Polwarth Building, Foresterhill, Aberdeen AB25 22D, United Kingdom. m.a.vickers@abdn.ac.uk
Canning
Sarah J
SJ
Craig
Wendy L
WL
Masson
Neil M
NM
Wilson
Ian J
IJ
D000328:Adult; D053687:Adult Stem Cells / Q000378:metabolism / Q000502:physiology*; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008875:Middle Aged; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism; D014680:Veins / Q000166:cytology / Q000378:metabolism; D049951:X Chromosome Inactivation
C410798:AR protein, human; D011944:Receptors, Androgen; D004247:DNA