Estimating the number of hematopoietic or lymphoid stem cells giving rise to clonal chromosome aberrations in blood T lymphocytes.
Quantifying the proliferative capacity of long-term hematopoietic stem cells in humans is important for bone marrow transplantation and gene therapy. Obtaining appropriate data is difficult, however, because the experimental tools are limited. We hypothesized that tracking clonal descendants originating from hematopoietic stem cells would be possible if we used clonal chromosome aberrations as unique tags of individual hematopoietic stem cells in vivo. Using FISH, we screened 500 blood T lymphocytes from each of 513 atomic bomb survivors and detected 96 clones composed of at least three cells with identical aberrations. The number of clones was inversely related to their population size, which we interpreted to mean that the progenitor cells were heterogeneous in the number of progeny that they could produce. The absolute number of progenitor cells contributing to the formation of the observed clones was estimated as about two in an unexposed individual. Further, scrutiny of ten clones revealed that lymphocyte clones could originate roughly equally from hematopoietic stem cells or from mature T lymphocytes, thereby suggesting that the estimated two progenitor cells are shared as one hematopoietic stem cell and one mature T cell. Our model predicts that one out of ten people bears a non- aberrant clone comprising >10% of the total lymphocytes, which indicates that clonal expansions are common and probably are not health-threatening.
Nakano
M
M
Department of Genetics, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815, Japan. Mimako_Nakano@rerf.or.jp
Kodama
Y
Y
Ohtaki
K
K
Itoh
M
M
Awa
A A
AA
Cologne
J
J
Kusunoki
Y
Y
Nakamura
N
N
D000293:Adolescent; D000328:Adult; D000375:Aging; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000235:genetics / Q000528:radiation effects; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000235:genetics / Q000528:radiation effects*; D003001:Cloning, Molecular / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D019143:Evolution, Molecular; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology* / Q000528:radiation effects*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007223:Infant; D008214:Lymphocytes / Q000473:pathology* / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015233:Models, Statistical; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017741:Survivors; D013601:T-Lymphocytes / Q000473:pathology* / Q000528:radiation effects*