Coexpression of platelet-derived growth factor receptor alpha and fetal liver kinase 1 enhances cardiogenic potential in embryonic stem cell differentiation in vitro
Coexpression of platelet-derived growth factor receptor alpha and fetal liver kinase 1 enhances cardiogenic potential in embryonic stem cell differentiation in vitro
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DOI：
10.1263/jbb.103.412
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发表时间：
2007-05-01
影响因子：
2.8
通讯作者：
Sawa, Yoshiki
中科院分区：
文献类型：
--
作者：
Hirata, Hirokazu;Kawamata, Shin;Sawa, Yoshiki
根据血小板衍生生长因子受体α（PDGFR α）和胎肝激酶1（Flk-1）的表达水平，对源自EB 5胚胎干（ES）细胞的新生中胚层细胞的心源性潜能进行分选。将分选的细胞与OP 9基质细胞共培养以诱导终末分化为收缩性心脏集落。在Flk-1+/PDGFR α +组分中发现了大量的心脏集落。富集双阳性级分产生的心脏集落比Flk-1+/PDGFR α-级分多约5倍，比Flk-1-/PDGFR α +级分多约10倍。为了研究这些标记物在胚胎心脏发生中的参与，将从E7.5-7.75胚胎散布的细胞分级并接种在OP 9细胞上。Flk-1+/PDGFRa+组分的心源性电位显著增强。这些结果表明，一些共表达这些标志物的前体细胞选择性地参与心源性事件，并与这些标志物的ES细胞衍生的前体细胞的鉴定将有助于心肌细胞的细胞治疗的有效生产。
Nascent mesodermal cells derived from EB5 embryonic stem (ES) cells were sorted in terms of cardiogenic potential on the basis of their expression levels of platelet-derived growth factor receptor alpha (PDGFR alpha) and fetal liver kinase 1 (Flk-1). The sorted cells were cocultured with OP9 stromal cells to induce terminal differentiation into contractile cardiac colonies. A significant number of cardiac colonies were found in the Flk-1+/PDGFR alpha+ fraction. The enrichment double-positive fraction produced approximately fivefold more cardiac colonies than the Flk-1+/PDGFR alpha-fraction and 10-fold more than the Flk-1-/PDGFR alpha+ fraction. To investigate the involvement of these markers in embryonic cardiogenesis, the cells that disseminated from the E7.5-7.75 embryos were fractionated and seeded on OP9 cells. The cardiogenic potential was markedly enhanced in the Flk-1+/PDGFRa+ fraction. These results suggest that some of the precursor cells coexpressing these markers are selectively involved in cardiogenic events, and that the identification of ES-cell-derived precursors with these markers will contribute to the effective production of cardiomyocytes for cell therapies.