Weisel Katja C, Gao Ying, Shieh Jae-Hung, Moore Malcolm A S
Laboratory of Developmental Hematopoiesis, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Exp Hematol. 2006 Nov;34(11):1505-16. doi: 10.1016/j.exphem.2006.06.013.
The hematopoietic system is nurtured by a supportive stroma environment allowing maintenance and differentiation of hematopoietic stem cells (HSC). However, only a limited number of these stromal cell clones support hematopoiesis in the absence of cytokine supplementation. So far, only two bone marrow-derived stromal cell lines (OP9 and S17) are capable of inducing hematopoietic differentiation of totipotent murine and human embryonic stem cells (ESC). Here, the potential of more than 100 stromal cell lines developed from the aorta-gonado-mesonephros (AGM) region was investigated in supporting adult and embryonic hematopoiesis. In addition, extensive phenotypic analysis should elucidate possible mechanisms involved in maintenance of hematopoietic stem cell function.
More than 100 stromal cell clones derived from the AGM region of E10.5 mouse embryos were isolated. Hematopoietic stem cell support was tested for adult murine and human cord blood hematopoietic stem cells and hematopoietic cells derived from murine ESC. Genotypic and phenotypic characterization was performed including gene array analysis.
It was demonstrated that multiple clones showed high efficiency in supporting maintenance and expansion of primitive murine and human hematopoietic progenitors. In addition, we demonstrated for the first time that AGM stromal cell lines are also potent inducers of hematopoietic differentiation of murine ESC. Microarray analysis of AGM lines revealed a characteristic genotype with expression of genes involved in regulating hematopoiesis as well as mesodermal and early B cell development.
These AGM stromal cell lines may be of value in elucidating molecular mechanisms regulating early stem cell development and hematopoietic differentiation from ES-derived mesoderm.
造血系统由支持性的基质环境滋养，该环境允许造血干细胞（HSC）的维持和分化。然而，在不添加细胞因子的情况下，只有有限数量的这些基质细胞克隆支持造血。到目前为止，只有两种骨髓来源的基质细胞系（OP9和S17）能够诱导全能小鼠和人类胚胎干细胞（ESC）的造血分化。在此，研究了从主动脉-性腺-中肾（AGM）区域发育而来的100多个基质细胞系在支持成人和胚胎造血方面的潜力。此外，广泛的表型分析应阐明参与维持造血干细胞功能的可能机制。
分离出100多个源自E10.5小鼠胚胎AGM区域的基质细胞克隆。对成年小鼠和人类脐带血造血干细胞以及源自小鼠ESC的造血细胞进行造血干细胞支持测试。进行了基因分型和表型特征分析，包括基因阵列分析。
证明多个克隆在支持原始小鼠和人类造血祖细胞的维持和扩增方面具有高效率。此外，我们首次证明AGM基质细胞系也是小鼠ESC造血分化的有效诱导剂。AGM系的微阵列分析揭示了一种特征性基因型，其表达参与调节造血以及中胚层和早期B细胞发育的基因。
这些AGM基质细胞系可能在阐明调节早期干细胞发育和ES衍生中胚层造血分化的分子机制方面具有价值。
