Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration
Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration
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DOI：
10.1242/jcs.006122
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发表时间：
2007-05-15
影响因子：
4
通讯作者：
Oh, Hidemasa
中科院分区：
文献类型：
--
作者：
Tateishi, Kento;Ashihara, Eishi;Oh, Hidemasa
最近的研究表明，来自成年哺乳动物心脏的心脏干细胞（CSCs）可以产生功能性心肌细胞;然而，到目前为止，确定的表面标志物，以确定一个明确的单一实体的CSCs和调控其生长的分子机制是未知的。在这里，我们展示了一种单细胞沉积分析，以分离成年小鼠心脏中单独选择的CSC，并研究其增殖和存活所需的信号。克隆增殖的CSC表达具有胚胎干（ES）细胞样和间充质细胞样特征的干细胞抗原-1（Sca-1），并且与端粒酶逆转录酶（TERT）相关。使用在TERT启动子控制下表达GFP报告基因的转基因，我们证明了来自心脏的TERTGFP阳性组分富集了表达Sca-1的细胞。CSCs中Sca-1转录物的敲低通过Akt失活导致离体扩增和凋亡延迟。我们还表明，直接细胞移植到缺血心肌后，持续CSC增殖和生存需要Sca-1上调分泌的旁分泌效应物，增加新血管生成和限制心脏凋亡。因此，Sca-1可能是促进CSC增殖和存活的重要成分，直接促进早期植入，并可能间接影响CSC移植后的晚期心血管分化。
Recent studies have shown that cardiac stem cells (CSCs) from the adult mammalian heart can give rise to functional cardiomyocytes; however, the definite surface markers to identify a definitive single entity of CSCs and the molecular mechanisms regulating their growth are so far unknown. Here, we demonstrate a single-cell deposition analysis to isolate individually selected CSCs from adult murine hearts and investigate the signals required for their proliferation and survival. Clonally proliferated CSCs express stem cell antigen-1 (Sca-1) with embryonic stem (ES) cell-like and mesenchymal cell-like characteristics and are associated with telomerase reverse transcriptase (TERT). Using a transgene that expresses a GFP reporter under the control of the TERT promoter, we demonstrated that TERTGFP-positive fractions from the heart were enriched for cells expressing Sca-1. Knockdown of Sca-1 transcripts in CSCs led to retarded ex vivo expansion and apoptosis through Akt inactivation. We also show that ongoing CSC proliferation and survival after direct cellgrafting into ischemic myocardium require Sca-1 to upregulate the secreted paracrine effectors that augment neoangiogenesis and limit cardiac apoptosis. Thus, Sca-1 might be an essential component to promote CSC proliferation and survival to directly facilitate early engraftment, and might indirectly exert the effects on late cardiovascular differentiation after CSC transplantation.