SDF-1/CXCL12 enhances survival and chemotaxis of murine embryonic stem cells and production of primitive and definitive hematopoietic progenitor cells
SDF-1/CXCL12 enhances survival and chemotaxis of murine embryonic stem cells and production of primitive and definitive hematopoietic progenitor cells
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DOI：
10.1634/stemcells.2005-0085
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发表时间：
2005-10-01
期刊：
影响因子：
5.2
通讯作者：
Broxmeyer, HE
中科院分区：
文献类型：
--
作者：
Guo, Y;Hangoc, G;Broxmeyer, HE
了解胚胎干细胞(ESC)的调控对于认识如何在体外最好地控制其生长和分化以获得潜在的治疗益处是重要的。基质细胞衍生因子-1(SDF-1/CXCL12)及其受体CXCR4被认为是许多胎儿和成人细胞功能的重要调节因子，包括造血干/祖细胞的存活/抗凋亡和迁移/归巢。我们推测SDF-1/CXCL12-CXCR4轴对小鼠胚胎干细胞功能的调节也是重要的。ESCs分泌低水平的SDF-1/CXCL12和低水平的CXCR4，但两者都随着ESCs的分化而增加。内源性产生/释放的SDF-1/CXCL12在有白血病抑制因子存在但无血清的情况下可促进ESCs的存活/抗凋亡，外源性SDF-1/CXCL12可进一步增强ESCs的存活/抗凋亡作用。此外，SDF-1/CXCL12可诱导ESCs的趋化，并可通过Diprotin A抑制CD26/二肽基肽酶IV而增强其趋化作用。内源性和外源性SDF-1/CXCL12促进原始和确定的红系、粒细胞-巨噬细胞和多潜能祖细胞的类胚体生成。SDF-1/CXCL12对血管母细胞的生成无明显影响。这些结果表明SDF-1/CXCL12对小鼠ESCs的存活、趋化和造血分化的功能活性可能与其体外操作有关。
Understanding embryonic stem cell (ESC) regulation is important for realizing how best to control their growth and differentiation ex vivo for potential therapeutic benefit. Stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptor, CXCR4, have been implicated as important regulators of a number of fetal and adult cell functions, including survival/antiapoptosis and migration/homing of hematopoietic stem and progenitor cells. We hypothesized that the SDF-1/ CXCL12-CXCR4 axis would also be important for regulation of murine ESC functions. ESCs secreted low levels of SDF-1/CXCL12 and expressed low levels of CXCR4; however, both increased with differentiation of ESCs. Endogenously produced/released SDF-1/CXCL12 enhanced survival/antiapoptosis of ESCs in the presence of leukemia inhibitory factor but absence of serum, and survival/antiapoptosis was further enhanced by exogenous administration of SDF-1/ CXCL12. Furthermore, SDF-1/CXCL12 induced chemotaxis of ESCs, and chemotaxis could be enhanced by diprotin A inhibition of CD26/dipeptidylpeptidase IV. Endogenous and exogenous SDF-1/CXCL12 enhanced embryoid body production of primitive and definitive erythroid, granulocyte-macrophage, and multipotential progenitors. SDF-1/CXCL12 did not noticeably affect production of hemangioblasts. These results demonstrate functional activities of SDF-1/CXCL12 on survival, chemotaxis, and hematopoietic differentiation of murine ESCs that may be relevant for their ex vivo manipulation.