Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts
Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts
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DOI：
10.1038/srep31457
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发表时间：
2016-08-19
影响因子：
4.6
通讯作者：
Schwartz, Robert J.
中科院分区：
文献类型：
--
作者：
Liu, Yu;Chen, Li;Schwartz, Robert J.
Mesp1 指导多能心血管细胞的命运，尽管它是在心脏祖细胞程序出现之前短暂诱导的。追踪 Mesp1 表达细胞及其后代可以分离和表征最早的心血管祖细胞。研究细胞培养和缺血性疾病模型中 Mesp1-CPC 的生物学特性是将其用于心脏病治疗的重要的第一步。由于Mesp1的短暂性，通过跟踪小鼠Mesp1(Cre/+)中的EYFP表达来追踪Mesp1-CPC谱系； Rosa26(EYFP/+) ES细胞。我们捕获了强烈表达心脏中胚层标记和心脏转录因子的 EYFP+ 细胞，但不表达多能或新生中胚层标记。 BMP2/4 处理导致 EYFP+ 细胞扩增，而 Wnt3a 和 Activin 效果有限。 BMP2/4 暴露很容易导致 EYFP+ 细胞分化为内皮细胞和平滑肌细胞，但需要抑制经典 Wnt 信号传导才能进入心肌细胞命运。注射小鼠预收缩 Mesp1-EYFP+ CPC 可提高受伤小鼠的生存能力，并恢复梗塞心脏的功能性能至少 3 个月。 Mesp1-EYFP+细胞是真正的CPC，它们在梗塞心脏中整合良好，并从头形成终末分化的心肌细胞、平滑肌和血管内皮细胞。
Mesp1 directs multipotential cardiovascular cell fates, even though it's transiently induced prior to the appearance of the cardiac progenitor program. Tracing Mesp1-expressing cells and their progeny allows isolation and characterization of the earliest cardiovascular progenitor cells. Studying the biology of Mesp1-CPCs in cell culture and ischemic disease models is an important initial step toward using them for heart disease treatment. Because of Mesp1's transitory nature, Mesp1-CPC lineages were traced by following EYFP expression in murine Mesp1(Cre/+); Rosa26(EYFP/+) ES cells. We captured EYFP+ cells that strongly expressed cardiac mesoderm markers and cardiac transcription factors, but not pluripotent or nascent mesoderm markers. BMP2/4 treatment led to the expansion of EYFP+ cells, while Wnt3a and Activin were marginally effective. BMP2/4 exposure readily led EYFP+ cells to endothelial and smooth muscle cells, but inhibition of the canonical Wnt signaling was required to enter the cardiomyocyte fate. Injected mouse pre-contractile Mesp1-EYFP+ CPCs improved the survivability of injured mice and restored the functional performance of infarcted hearts for at least 3 months. Mesp1-EYFP+ cells are bona fide CPCs and they integrated well in infarcted hearts and emerged de novo into terminally differentiated cardiac myocytes, smooth muscle and vascular endothelial cells.