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

Kenji Kawabata, Miho Ujikawa, Takeshi Egawa, Hiroshi Kawamoto, Kazunobu Tachibana, Hisashi Iizasa, Yoshimoto Katsura, Tadamitsu Kishimoto, Takashi Nagasawa

Research output: Contribution to journalArticlepeer-review

194 Citations (Scopus)

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+ lin(low/-) cells by CXCR4(-/-) fetal liver cells was less affected compared with c-kit+ Sca-1-lin(low/-) cells. By previous studies, it has been shown that c-kit+ Sea-1+ lin(low/-) cells are highly purified primitive hematopoietic progenitors and that c-kit+ Sca- 1- lin(low/-) 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.

Original languageEnglish
Pages (from-to)5663-5667
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number10
DOIs
Publication statusPublished - 11-05-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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