Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny

Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny
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DOI:
10.1016/s1074-7613(03)00201-2
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发表时间:
2003-08-01
期刊:
影响因子:
32.4
通讯作者:
Nagasawa, T
Nagasawa, T
中科院分区:
医学1区
文献类型:
--
作者:
Ara, T;Tokoyoda, K;Nagasawa, T

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SDF-1 对造血干细胞 (HSC) 的生理作用仍不清楚。我们通过长期再增殖测定表明,在 SDF-1(-/-) 胚胎中,除了骨髓细胞外,HSC 的骨髓定植也受到严重损害。造血干细胞对脾脏的定植也受到影响,但程度较小。在血管特异性Tie-2调控序列的控制下强制表达SDF-1可以完全挽救HSC的减少,但不能挽救SDF-1(-/-)骨髓中骨髓细胞的减少。在胎儿骨髓中血管内皮细胞附近检测到SDF-1。 SDF-1 在个体发育过程中 HSC 和骨髓细胞在骨髓中的定植中发挥着关键作用,并且 SDF-1 的功能机制在 HSC 和骨髓细胞之间是不同的。
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.