Hirota Saeka, Ogawa Minetaro
Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
Biochem Biophys Res Commun. 2015 Nov 20;467(3):583-8. doi: 10.1016/j.bbrc.2015.09.131. Epub 2015 Sep 28.
Lateral mesoderm-derived hemogenic endothelial cells are known to originate the definitive hematopoietic lineage in mouse embryogenesis. The developmental process of the definitive hematopoietic lineage can be recapitulated by inducing differentiation of mouse embryonic stem (ES) cells in a co-culture system with OP9 stromal cells. However, the signaling molecules that can modulate the development of the definitive hematopoietic lineage in the OP9 co-culture system have yet to be identified. Here we report that activin A enhanced the hematopoietic potential of endothelial cells derived from ES cells in the OP9 co-culture system. Activin A in combination with OP9 cells augmented development of Flk-1(+) PDGFRα(+) early mesodermal cells and Flk-1(+) PDGFRα(-) lateral mesodermal cells from ES cells. These Flk-1(+) mesodermal cells further differentiated into CD41(+) endothelial cells, which preferentially possessed high hematopoietic potential. Furthermore, Flk-1(+) PDGFRα(+) cells but not Flk-1(+) PDGFRα(-) cells produced hematopoietic progenitors with a bimodal pattern when cultured as an aggregate with OP9 cells. Our results suggest that activin A in combination with OP9 cells facilitates differentiation of ES cells to Flk-1(+) mesodermal cells, which encompass various precursors that separately contribute to the development of hematopoietic lineages.
已知在小鼠胚胎发育过程中，侧向中胚层来源的造血内皮细胞可产生定型造血谱系。在与OP9基质细胞的共培养系统中诱导小鼠胚胎干细胞（ES细胞）分化，可重现定型造血谱系的发育过程。然而，在OP9共培养系统中，能够调节定型造血谱系发育的信号分子尚未得到鉴定。在此，我们报告激活素A增强了OP9共培养系统中ES细胞来源的内皮细胞的造血潜能。激活素A与OP9细胞共同作用，增强了ES细胞中Flk-1(+) PDGFRα(+)早期中胚层细胞和Flk-1(+) PDGFRα(-)侧向中胚层细胞的发育。这些Flk-1(+)中胚层细胞进一步分化为CD41(+)内皮细胞，这些内皮细胞优先具有较高的造血潜能。此外，当与OP9细胞聚集成团培养时，Flk-1(+) PDGFRα(+)细胞而非Flk-1(+) PDGFRα(-)细胞会以双峰模式产生造血祖细胞。我们的结果表明，激活素A与OP9细胞共同作用促进了ES细胞向Flk-1(+)中胚层细胞的分化，这些中胚层细胞包含各种前体细胞，它们分别对造血谱系的发育做出贡献。
