EXPRESSION OF MURINE CD38 DEFINES A POPULATION OF LONG-TERM RECONSTITUTING HEMATOPOIETIC STEM-CELLS

Using a monoclonal antibody to murine CD38, we showed that a populatio n of adult bone marrow cells that expressed the markers Sca-1 and c-ki t but lacked the lineage markers Mac-1, GR-1, B220, IgM, CD3, CD4, CD8 and CD5 could be subdivided by the expression of CD38. We showed that CD38(high) c-kit(+) Sca-1(+), lin(low/-) cells sorted from adult bone marrow cultured with interleukin-3 (IL-3), IL-6, and kit-L produced m uch larger colonies in liquid culture at a greater frequency than thei r CD38(low/-) counterparts. In addition, we found that CD38(low/-) cel ls contained most of the day-12 colony-forming units-spleen (CFU-S) bu t were not long-term reconstituting cells, whereas the population that expressed higher levels of CD38 contained few, but significant, day-1 2 CFU-S and virtually all the long-term reconstituting stem cells. Int erestingly, the CD38(high) Sca1(+) C-kit(+) lin(low/-) cells isolated from day-E14.5 fetal liver were also found to be long-term reconstitut ing stem cells. This is in striking contrast to human hematopoietic pr ogenitors in which the most primitive hematopoietic cells from fetal t issues lack the expression of CD38. Furthermore, because antibodies to CD38 could functionally replace antibodies to Thy-1.1 in a stem cell purification procedure, the use of anti-CD38 may be more generally app licable to the purification of hematopoietic stem cells from mouse str ains that do not express the Thy-1.1 allele. (C) 1996 by The American Society of Hematology.