Hemopoietic precursor cell defects in nonanemic but stem cell-deficient W44/W44 mice

Area of Science:

• Hematology
• Stem Cell Biology
• Genetics

Background:

• W/Wv mice exhibit severe macrocytic anemia due to hematopoietic stem cell deficiencies.
• W44/W44 mice, while not anemic, possess a stem cell defect allowing marrow engraftment without irradiation.

Purpose of the Study:

• To identify aberrant stem cells in W44/W44 mice.
• To determine the concentration of hematopoietic precursors in W44/W44 marrow compared to W/Wv marrow.

Main Methods:

• Assessed in vitro erythroid burst-forming units (BFU-E).
• Examined in vivo spleen colony-forming units (CFU-S).
• Evaluated cells repopulating erythroid compartments in stem cell-deficient mice.

Main Results:

• BFU-E progenitors were reduced in W/Wv but normal in W44/W44 marrow.
• W44/W44 marrow CFU-S formed smaller, less numerous spleen colonies than +/+ marrow.
• W44/W44 stem cells showed impaired competitive repopulation of erythroid compartments.

Conclusions:

• A defect in an erythroid progenitor, less mature than BFU-E, is implicated in W44/W44 mice.
• W44/W44 mice may have up to 10-fold fewer functional stem cells in the erythrogenerative pathway.