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Blood, 15 December 2000, Vol. 96, No. 13, pp. 4124-4131
HEMATOPOIESIS
Primitive hematopoietic stem cell function in vivo is
uniquely high in the CXB-12 mouse strain
Jichun Chen,
Clinton M. Astle,
Christa E. Müller-Sieburg, and
David E. Harrison
From The Jackson Laboratory, Bar Harbor, ME;
and the Sidney Kimmel Cancer Center, San Diego, CA.
Bone marrow cells (BMCs) from CXB-12/HiaJ (CXB-12) mice had 14 times the total long-term repopulating ability found in the best of 11 other CXB recombinant inbred (RI) lines. BMCs from each RI line donor
were mixed with genetically marked standard competitor BMCs from the
BALB/cBy×C57BL/6 F1 (CByB6F1) hybrid, the mice used to produce the RI
lines, and the mixtures repopulated lethally irradiated CByB6F1
recipients. Percentages of donor-type erythrocytes and lymphocytes
measured the actual long-term repopulating functions of the donor RI
lines relative to the standard competitor. CXB-12 BMCs repopulated
better after 3 or 6 months than after 1 month, suggesting that the most
primitive precursors were involved. Compared to CByB6F1 standard
competitor cells, CXB-12 cells repopulated 3 to 12 times as well, with
their advantage increasing when higher doses of cells were
transplanted, probably because of hybrid resistance of the recipient
against low doses. This was far better than expected, because F1 cells
normally function 2 to 3 times as well as cells from an inbred strain.
In competitive dilution, the advantage resulted from 2 factors: more
precursor cells and more function per precursor. In the model that best
fit the data, CXB-12 donors had 2.4 times the concentration of
hematopoietic stem cells (HSCs) as the CByB6F1 standard, and each HSC
repopulated 1.4 times as well. CXB-12 mice did not have elevated
erythrocyte and lymphocyte numbers in blood and marrow and did not have
unusually elevated concentrations of colony-forming unit spleen,
cobblestone colonies, and long-term colony-initiating cells in marrow.
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