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Large numbers of primitive stem cells are active simultaneously in
aggregated embryo chimeric mice
DE Harrison, C Lerner, PC Hoppe, GA Carlson and D Alling
The possibility has been repeatedly raised that erythropoiesis results from
clonal succession--the differentiation of one or a very small number of the
most primitive stem cells that are sequentially activated to proliferate
forming clones of differentiated cells and then eventually decline, to be
replaced by new stem cell clones. We studied this possibility in chimeric
mice made by combining embryos from two different strains so that they
would have two distinct stem cell populations, each of which produces a
different hemoglobin type (d and s). These were compared with F1 hybrids in
which every stem cell produces both types. We measured the percentage of
type d in seven to ten serial samples of circulating reticulocytes taken at
three- to seven-day intervals and found that the variability in percent of
this hemoglobin was only slightly higher in the chimeric mice than in F1
controls; SD ranged from 2.7% to 5.5% in the chimeric mice and from 3.4% to
3.9% in the controls. Using the binomial formula, the numbers of new clones
formed during the reticulocyte life span, approximately three days, ranged
from 33 to 118 in the individual chimeric mice. However, these numbers are
underestimates because estimated numbers of clones depend inversely on
variabilities, and the calculations did not exclude the contribution of
experimental error to the overall variability. Total percentages of type d
hemoglobin were also measured in seven to nine successive serial samples at
60- to 136-day intervals. These gave mean values similar to measures of
newly synthesized hemoglobin in the same mice, but SD were larger, ranging
from 5.3% to 8.4%. This reflects experimental error, both because of excess
day-to- day variability found in this type of measurement and because there
could not be fewer primitive stem cells activated to form clones of
erythrocytes during the 45-day erythrocyte life span than during the
three-day life span of reticulocytes. Since most and maybe all of the
variation between successive samples in the same chimeric mouse appear to
result from experimental error, many or even all of the primitive stem
cells may simultaneously contribute to erythropoiesis.
Volume 69,
Issue 3,
pp. 773-777,
03/01/1987
Copyright © 1987 by The American Society of Hematology
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