2003 Fiscal Year Final Research Report Summary
The role of chemokine CXCL12 (SDF-1/PBSF) in hematopoiesis and blood vessel formation.
| Project/Area Number |
11235204
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
| Allocation Type | Single-year Grants |
|---|
| Review Section |
Biological Sciences
|
|---|
| Research Institution | Kyoto University (2002-2003)
Research Institute, Osaka Medical Center for Maternal and Child Health (1999-2001) |
|---|
Principal Investigator |
TAKASHI Nagasawa TAKASHI,Nagasawa, 再生医科学研究所, 教授 (80281690)
|
|---|
| Project Period (FY) |
1999 – 2002
|
| Keywords | chemokine / lymphocyte / hematopoiesis / hematopoietic stem cell / homing / niche / primordial germ cells |
|---|
| Research Abstract |
(1) CXCL12 might regulate the movement of progenitors within the organ during development We have identified the earliest B cell precursors in fetal liver and have shown that these precursors require CXC chemokine ligand (CXCL) 12. These results raise the possibility that diverse lineages., of hematopoietic precursors which arise from common multipotent progenitors move toward CXCL12 and stabilize in presumptive specific niches for the lineages. We are studying the niches for lymphopoiesis and the molecular mechanisms by which CXCL12 plays a role in hematopoiesis and blood vessel formation using the purified precursors.
(2) CXCL12 is essential for the horning of stem cells and progenitors to the organs during development. We have shown that the numbers of hematopoietic stem cells (HSCs) are normal in feta liver, but severe]y reduced in fetal bone marrow and increased in peripheral blood in CXCL12^<-/-> embryos, indicating that CXCL12 plays a critical role in colonization of bone marroww by HSCs during ontogeny. Enforced explession of CXCL12 under the control of vascular-specific Tie-2 regulatory sequences could completely rescue the reduction of HSCs in CXCL12^<-/-> bone marrow, suggesting that CXCL12 adjacent to endothelial cells plays a role in the colonization of bone marrow by HSCs. In consistent with this, CXCL12-expressing cells were located in the vicinity of the vascular endothelial cells in fetal bone marrow. On the other hand, we have shown that in CXCL12^<-/-> embryos primordial germ cells (PGCs) which migrate through the tissues of the embryos and colonize the gonads during development undergo directed migration through tissues of embryos but the numbers of PGCs in the gonads are significantly reduced, revealing the essential role for CXCL12 in murine PGC development likely by controlling colonization of the gonads by PGCs. Together, we have shown that CXCL12 is essential for colonization of organs by tissue-specific stem cells during development.
|
