Center of Basic Research, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou St., Athens, 11527, Greece.
Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou St., Athens, 11527, Greece.
Cell Tissue Res. 2022 Aug;389(2):309-326. doi: 10.1007/s00441-022-03643-8. Epub 2022 Jun 4.
The heart's limited regenerative capacity raises the need for novel stem cell-based therapeutic approaches for cardiac regeneration. However, the use of stem cells is restrictive due to poor determination of their properties and the factors that regulate them. Here, we investigated the role of desmin, the major muscle-specific intermediate filament protein, in the characteristics and differentiation capacity of cardiac side population (CSP) and Sca1 stem cells of adult mice. We found that desmin deficiency affects the microenvironment of the cells and leads to increased numbers of CSP but not Sca1 cells; CSP subpopulation composition is altered, the expression of the senescence marker p16 in Sca1 cells is increased, and early cardiomyogenic commitment is impaired. Specifically, we found that mRNA levels of the cardiac transcription factors Mef2c and Nkx2.5 were significantly reduced in des CSP and Sca1 cells, while differentiation of CSP and Sca1 cells demonstrated that in the absence of desmin, the levels of Nkx2.5, Mef2c, Tnnt2, Hey2, and Myh6 mRNA are differentially affected. Thus, desmin deficiency restricts the regenerative potential of CSP and Sca1 cells, both directly and indirectly through their microenvironment.
心脏的有限再生能力提出了对新型基于干细胞的心脏再生治疗方法的需求。然而，由于难以确定其特性和调节它们的因素，干细胞的应用受到限制。在这里，我们研究了结蛋白（主要的肌肉特异性中间丝蛋白）在成年小鼠心脏侧群（CSP）和 Sca1 干细胞的特性和分化能力中的作用。我们发现，结蛋白缺乏会影响细胞的微环境，导致 CSP 数量增加，但 Sca1 细胞数量没有增加；CSP 亚群组成发生改变，Sca1 细胞中衰老标志物 p16 的表达增加，早期心肌生成承诺受损。具体而言，我们发现心脏转录因子 Mef2c 和 Nkx2.5 的 mRNA 水平在缺失结蛋白的 CSP 和 Sca1 细胞中显著降低，而 CSP 和 Sca1 细胞的分化表明，在缺乏结蛋白的情况下，Nkx2.5、Mef2c、Tnnt2、Hey2 和 Myh6 的 mRNA 水平受到不同程度的影响。因此，结蛋白缺乏会直接和间接地通过其微环境限制 CSP 和 Sca1 细胞的再生潜力。
