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Hemopoietic precursor cell defects in nonanemic but stem cell‐deficient W 44 / W 44 mice
Author(s) -
Barker Jane E.,
McFarland Eleanor C.
Publication year - 1988
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041350324
Subject(s) - haematopoiesis , stem cell , microbiology and biotechnology , progenitor cell , biology , bone marrow , chemistry , immunology
Hematopoietic stem cell deficiencies cause a severe macrocytic anemia in W / W ″ mice. W 44 / W 44 mice, on the other hand, are not anemic, but, since they accept marrow implants without prior total body irradiation, they have inherited a stem cell lesion. In an attempt to identify the aberrant stem cell(s), we have determined the concentration in W 44 / W 44 marrow of hematopoietic precursors known to be deficient in W / W v marrow. The in vitro erythroid burst‐forming units (BFU‐E), the in vivo spleen colony‐forming units (CFU‐S), and the cells that repopulate the erythroid compartment of stem cell‐deficient mice were examined. The progenitors of 7‐day bursts are dramatically reduced in W/W″ marrow but are present in normal concentrations in W 44 / W 44 marrow. W 44 / W 44 marrow CFU‐S, unlike W/W″, generate visible spleen colonies 10 days after injection into lethally irradiated recipients. The colonies are, however, smaller and at least 2 times less numerous than those produced from equivalent numbers of +/+ marrow. An additional defect was the inability of W 44 / W 44 stem cells to compete with genetically marked +/+ cells during erythroid repopulation. An estimate of the number of W 44 / W 44 stem cells needed to compete with +/+ cells was provided by enriching W 44 / W 44 progenitors fivefold. Twice as many enriched W 44 / W 44 marrow cells as unfractionated +/+ cells were required to replace competitor cells. This suggests that there are up to 10 times fewer stem cells somewhere in the W 44 / W 44 erythrogenerative pathway. The data support the conclusion that an erythroid progenitor less mature than the BFU‐E is one of the cells most severely affected by expression of the mutant gene.