Single-cell-derived mesenchymal stem cells overexpressing Csx/Nkx2.5 and GATA4 undergo the stochastic cardiomyogenic fate and behave like transient amplifying cells.
Single-cell-derived mesenchymal stem cells overexpressing Csx/Nkx2.5 and GATA4 undergo the stochastic cardiomyogenic fate and behave like transient amplifying cells.
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DOI：
10.1016/j.yexcr.2006.11.012
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发表时间：
2007-02
影响因子：
3.7
通讯作者：
Yoji Yamada;K. Sakurada;Yukiji Takeda;S. Gojo;A. Umezawa
中科院分区：
文献类型：
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作者：
Yoji Yamada;K. Sakurada;Yukiji Takeda;S. Gojo;A. Umezawa
骨髓来源的基质细胞可以在体外产生心肌细胞以及脂肪细胞、骨细胞和软骨细胞。间充质干细胞的存在已被提出，但尚不清楚单细胞衍生的干细胞是否随机地定向为心脏谱系。通过单细胞标记，我们对源自骨髓细胞的 9-15c 间充质基质细胞分化过程中的单个细胞进行了跟踪研究。从单个细胞分化出三种类型的细胞，即心脏成肌细胞、心脏祖细胞和多能干细胞，这意味着心肌细胞是由单细胞来源的干细胞随机产生的。我们还证明，Csx/Nkx2.5和GATA4、心前中胚层转录因子的过表达可增强9-15c细胞的心肌分化，并且通过与胎儿心肌细胞共培养，心肌分化的频率增加。过表达Csx/Nkx2.5和GATA4的单细胞来源的间充质干细胞表现得像心脏瞬时放大细胞，并且在体内仍然保留其可塑性。
Bone marrow-derived stromal cells can give rise to cardiomyocytes as well as adipocytes, osteocytes, and chondrocytes in vitro. The existence of mesenchymal stem cells has been proposed, but it remains unclear if a single-cell-derived stem cell stochastically commits toward a cardiac lineage. By single-cell marking, we performed a follow-up study of individual cells during the differentiation of 9-15c mesenchymal stromal cells derived from bone marrow cells. Three types of cells, i.e., cardiac myoblasts, cardiac progenitors and multipotent stem cells were differentiated from a single cell, implying that cardiomyocytes are generated stochastically from a single-cell-derived stem cell. We also demonstrated that overexpression of Csx/Nkx2.5 and GATA4, precardiac mesodermal transcription factors, enhanced cardiomyogenic differentiation of 9-15c cells, and the frequency of cardiomyogenic differentiation was increased by co-culturing with fetal cardiomyocytes. Single-cell-derived mesenchymal stem cells overexpressing Csx/Nkx2.5 and GATA4 behaved like cardiac transient amplifying cells, and still retained their plasticity in vivo.