A Cell-Autonomous Requirement for CXCR4 in Long-Term Lymphoid and Myeloid Reconstitution
Abstract
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.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- May 1999
- DOI:
- 10.1073/pnas.96.10.5663
- Bibcode:
- 1999PNAS...96.5663K