A cell-autonomous requirement for CXCR4 in long-term lymphoid and myeloid reconstitution

Mice lacking the chemokine stromal cell-derived factor/pre-B cell growth st imulating factor or its primary physiological receptor CXCR4 revealed defec ts in B lymphopoiesis and bone marrow myelopoiesis during embryogenesis, We show here that adoptive transfer experiments reveal a deficiency in long-t erm lymphoid and myeloid repopulation in adult bone marrow by CXC4-/- fetal liver cells, although stromal cell-derived factor/pre-B cell growth stimul ating factor-/- fetal liver cells yield normal multilineage reconstitution. These findings indicate that CXCR4 is required cell autonomously for lymph oid and myeloid repopulation in bone marrow. In addition, CXCR4-/- fetal li ver cells generated much more severely reduced numbers of B cells relative to other lineages in bone marrow, Furthermore, the repopulation of c-kit(+) Sca-1(+) lin(low/-) cells by CXCR4-/- fetal liver cells was less affected compared with c-kit(+) Sca-1(-) lin(low/-) cells, By previous studies, it h as been shown that c-kit(+) Sca-1(+) lin(low/-) cells are highly purified p rimitive hematopoietic progenitors and that c-kit(+) Sca-1(-) lin(low/-) ce lls are more committed hematopoietic progenitors in mice. Thus, CXCR4 may p lay an essential role in generation and/or expansion of early hematopoietic progenitors within bone marrow.