Genetic lineage tracing identifies in situ Kit-expressing cardiomyocytes.
Genetic lineage tracing identifies in situ Kit-expressing cardiomyocytes.
复制标题
遗传谱系追踪鉴定原位表达 Kit 的心肌细胞
DOI：
10.1038/cr.2015.143
复制
发表时间：
2016-01
期刊：
影响因子：
44.1
通讯作者：
Zhou B
中科院分区：
文献类型：
--
作者：
Liu Q;Yang R;Huang X;Zhang H;He L;Zhang L;Tian X;Nie Y;Hu S;Yan Y;Zhang L;Qiao Z;Wang QD;Lui KO;Zhou B
由c-Kit或Kit标记的心脏细胞，被称为心脏干细胞（CSC），正在进行临床试验，以研究它们刺激心脏再生和修复的能力。这些研究最初是由这些细胞的所谓的心源性活动的动机。最近使用Kit启动子驱动诱导型Cre重组酶表达的谱系追踪研究表明，这些CSC具有高度有限的心源性活性，不足以支持有效的心脏修复。在这里，我们重新评估的谱系跟踪数据，调查后立即Cre标记的细胞的身份。我们的即时谱系追踪方法鉴定了表达Kit的心肌细胞，其在他莫昔芬诱导后立即被标记。结合长期谱系追踪实验，这些数据表明，大多数长期标记的心肌细胞是预先存在的表达Kit的心肌细胞，而不是从CSC从头形成的心肌细胞。这项研究对Kit+细胞对心肌细胞的贡献提出了新的解释，并表明Kit遗传谱系追踪高估了Kit+ CSC的心源性活性。
Cardiac cells marked by c-Kit or Kit, dubbed cardiac stem cells (CSCs), are in clinical trials to investigate their ability to stimulate cardiac regeneration and repair. These studies were initially motivated by the purported cardiogenic activity of these cells. Recent lineage tracing studies using Kit promoter to drive expression of the inducible Cre recombinase showed that these CSCs had highly limited cardiogenic activity, inadequate to support efficient cardiac repair. Here we reassess the lineage tracing data by investigating the identity of cells immediately after Cre labeling. Our instant lineage tracing approach identifies Kit-expressing cardiomyocytes, which are labeled immediately after tamoxifen induction. In combination with long-term lineage tracing experiments, these data reveal that the large majority of long-term labeled cardiomyocytes are pre-existing Kit-expressing cardiomyocytes rather than cardiomyocytes formed de novo from CSCs. This study presents a new interpretation for the contribution of Kit+ cells to cardiomyocytes and shows that Kit genetic lineage tracing over-estimates the cardiogenic activity of Kit+ CSCs.