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 stimulating factor or its primary physiological receptor CXCR4 revealed defects in B lymphopoiesis and bone marrow myelopoiesis during embryogenesis. We show here that adoptive transfer experiments reveal a deficiency in long-term lymphoid and myeloid repopulation in adult bone marrow by CXCR4-/- fetal liver cells, although stromal cell-derived factor/pre-B cell growth stimulating factor-/- fetal liver cells yield normal multilineage reconstitution. These findings indicate that CXCR4 is required cell autonomously for lymphoid and myeloid repopulation in bone marrow. In addition, CXCR4-/- fetal liver 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(+) linlow/- cells by CXCR4-/- fetal liver cells was less affected compared with c-kit+ Sca-1(-) linlow/- cells. By previous studies, it has been shown that c-kit+ Sca-1(+) linlow/- cells are highly purified primitive hematopoietic progenitors and that c-kit+ Sca-1(-) linlow/- cells are more committed hematopoietic progenitors in mice. Thus, CXCR4 may play an essential role in generation and/or expansion of early hematopoietic progenitors within bone marrow.
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D002678:Chimera; D005434:Flow Cytometry; D007962:Leukocytes; D019891:Leukopoiesis / Q000235:genetics*; D008099:Liver / Q000196:embryology; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019718:Receptors, CXCR4 / Q000235:genetics*; D013154:Spleen / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism