Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny.
The physiological role of SDF-1 on hematopoietic stem cells (HSCs) remains elusive. We show that colonization of bone marrow by HSCs in addition to myeloid cells is severely impaired in SDF-1(-/-) embryos by a long-term repopulation assay. Colonization of spleen by HSCs was also affected, but to a lesser extent. Enforced expression of SDF-1 under the control of vascular-specific Tie-2 regulatory sequences could completely rescue the reduction of HSCs but not myeloid cells in SDF-1(-/-) bone marrow. SDF-1 was detected in the vicinity of the vascular endothelial cells in fetal bone marrow. SDF-1 plays a critical role in colonization of bone marrow by HSCs and myeloid cells during ontogeny, and the mechanisms by which SDF-1 functions are distinct between HSCs and myeloid cells.
Ara
Toshiaki
T
Department of Medical Systems Control, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Tokoyoda
Koji
K
Sugiyama
Tatsuki
T
Egawa
Takeshi
T
Kawabata
Kenji
K
Nagasawa
Takashi
T
D000818:Animals; D001853:Bone Marrow / Q000196:embryology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D015870:Gene Expression; D005809:Genes, Regulator; D006410:Hematopoiesis / Q000276:immunology / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D042787:Receptor, TIE-2
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2