Mouse and human induced pluripotent stem cells as a source for multipotent Isl1+ cardiovascular progenitors
Mouse and human induced pluripotent stem cells as a source for multipotent Isl1+ cardiovascular progenitors
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DOI：
10.1096/fj.09-139477
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发表时间：
2010-03-01
期刊：
影响因子：
4.8
通讯作者：
Laugwitz, Karl-Ludwig
中科院分区：
文献类型：
--
作者：
Moretti, Alessandra;Bellin, Milena;Laugwitz, Karl-Ludwig
确定的遗传因子集合的异位表达可以重编程体细胞以产生诱导多能干细胞（iPS）。将人iPS细胞定向至特定分化谱系及其祖细胞群体的能力可用于疾病建模、药物发现和最终的自体细胞替代疗法。在小鼠心脏发生过程中，成熟心脏、心肌细胞、平滑肌细胞和内皮细胞的主要谱系来自表达转录因子Isl1和Nkx2.5的共同的多能心血管祖细胞。在这里，我们显示，使用遗传命运作图，Isl1（+）多能心血管祖细胞可以从小鼠iPS细胞中产生，并在体内自发分化为所有3种心血管谱系，而没有畸胎瘤。此外，我们报告了具有相似发育潜力的人iPS衍生的ISL 1（+）祖细胞的鉴定。这些结果支持使用患者特异性iPS产生的心血管祖细胞作为模型来阐明先天性和获得性心脏病的发病机制的可能性。Moretti，A.，贝林，M.，荣格角，澳-地B.，Thies，T. M.，Takashima，Y.，Bernshausen，A.，Schiemann，M.，费希尔，S.，Moosmang，S.，史密斯，A. G.，Lam，J.T.，劳格维茨，K. - L.小鼠和人类诱导多能干细胞作为多能Isl1（+）心血管祖细胞的来源。FASEB J.24，700 - 711（2010）。www.fasebj.org
Ectopic expression of defined sets of genetic factors can reprogram somatic cells to create induced pluripotent stem (iPS) cells. The capacity to direct human iPS cells to specific differentiated lineages and to their progenitor populations can be used for disease modeling, drug discovery, and eventually autologous cell replacement therapies. During mouse cardiogenesis, the major lineages of the mature heart, cardiomyocytes, smooth muscle cells, and endothelial cells arise from a common, multipotent cardiovascular progenitor expressing the transcription factors Isl1 and Nkx2.5. Here we show, using genetic fate-mapping, that Isl1(+) multipotent cardiovascular progenitors can be generated from mouse iPS cells and spontaneously differentiate in all 3 cardiovascular lineages in vivo without teratoma. Moreover, we report the identification of human iPS-derived ISL1(+) progenitors with similar developmental potential. These results support the possibility to use patient-specific iPS-generated cardiovascular progenitors as a model to elucidate the pathogenesis of congenital and acquired forms of heart diseases.-Moretti, A., Bellin, M., Jung, C. B., Thies, T.-M., Takashima, Y., Bernshausen, A., Schiemann, M., Fischer, S., Moosmang, S., Smith, A. G., Lam, J. T., Laugwitz, K.-L. Mouse and human induced pluripotent stem cells as a source for multipotent Isl1(+) cardiovascular progenitors. FASEB J. 24, 700-711 (2010). www.fasebj.org