Department of Cell and Developmental Biology, Cardiovascular Institute and Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Circ Res. 2012 Mar 30;110(7):922-6. doi: 10.1161/CIRCRESAHA.112.266510. Epub 2012 Mar 6.
Islet1 (Isl1) has been proposed as a marker of cardiac progenitor cells derived from the second heart field and is utilized to identify and purify cardiac progenitors from murine and human specimens for ex vivo expansion. The use of Isl1 as a specific second heart field marker is dependent on its exclusion from other cardiac lineages such as neural crest.
Determine whether Isl1 is expressed by cardiac neural crest.
We used an intersectional fate-mapping system using the RC::FrePe allele, which reports dual Flpe and Cre recombination. Combining Isl1(Cre/+), a SHF driver, and Wnt1::Flpe, a neural crest driver, with Rc::FrePe reveals that some Isl1 derivatives in the cardiac outflow tract derive from Wnt1-expressing neural crest progenitors. In contrast, no overlap was observed between Wnt1-derived neural crest and an alternative second heart field driver, Mef2c-AHF-Cre.
Isl1 is not restricted to second heart field progenitors in the developing heart but also labels cardiac neural crest. The intersection of Isl1 and Wnt1 lineages within the heart provides a caveat to using Isl1 as an exclusive second heart field cardiac progenitor marker and suggests that some Isl1-expressing progenitor cells derived from embryos, embryonic stem cultures, or induced pluripotent stem cultures may be of neural crest lineage.
胰岛 1（Isl1）被提议作为源自第二心区的心脏祖细胞的标志物，并用于鉴定和纯化来自鼠和人标本的心脏祖细胞，以进行体外扩增。Isl1 作为特定的第二心区标志物的使用取决于其排除其他心脏谱系，如神经嵴。
确定 Isl1 是否表达于心脏神经嵴。
我们使用了一种交叉性命运映射系统，该系统使用了 RC::FrePe 等位基因，该基因报告双重 Flpe 和 Cre 重组。结合使用 Isl1(Cre/+), 一种 SHF 驱动子，和 Wnt1::Flpe, 一种神经嵴驱动子，与 Rc::FrePe 揭示了一些心脏流出道中的 Isl1 衍生物源自 Wnt1 表达的神经嵴祖细胞。相比之下，在 Wnt1 衍生的神经嵴和替代的第二心区驱动子 Mef2c-AHF-Cre 之间没有观察到重叠。
Isl1 不仅局限于发育心脏中的第二心区祖细胞，还标记心脏神经嵴。心脏内的 Isl1 和 Wnt1 谱系的交叉为将 Isl1 用作唯一的第二心区心脏祖细胞标志物提供了警示，并表明一些源自胚胎、胚胎干细胞培养或诱导多能干细胞培养的表达 Isl1 的祖细胞可能具有神经嵴谱系。
