Sandstedt Joakim, Jonsson Marianne, Vukusic Kristina, Dellgren Göran, Lindahl Anders, Jeppsson Anders, Asp Julia
Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Cells Tissues Organs. 2014;199(2-3):103-16. doi: 10.1159/000363225. Epub 2014 Aug 21.
Stage-specific embryonic antigen (SSEA) expression is used to describe the differentiation state of an embryonic stem cell (ESC). In human ESCs, SSEA-3 and SSEA-4 are highly expressed in undifferentiated cells and downregulated upon differentiation. SSEA-4 has also been described as a marker for adult stem cells in various tissues, including human neonatal cardiac tissue. However, there is currently little data on the expression of SSEAs in human adult cardiac tissue. We obtained right and left atrial biopsies from patients undergoing cardiac surgery. These were dissociated, stained for SSEAs and other cardiac stem cell markers and analyzed by flow cytometry. Directly isolated cells expressed variable levels of SSEA-1, SSEA-3 and SSEA-4. The SSEA-1+ population was established as contaminating hematopoietic cells. The SSEA-4+ population, on the other hand, could be subdivided based on the endothelial progenitor marker CD34. The SSEA-4+ CD34- population in the right atrium had a high gene expression of both early (TBX5, NKX2.5) and late (TNNT2) cardiomyocyte markers. The SSEA-4+ CD34+ population, on the other hand, overlapped with previously described C-kit+ CD45- cardiac stem cells. Primary monolayer-cultured cells retained expression of SSEAs while the cardiomyogenic specification in the SSEA-4+ CD34- population was lost. In tissue sections, SSEA-4+ cells could be identified both within and outside the myocardium. Within the myocardium, some SSEA-4+ cells coexpressed cardiomyogenic markers. In conclusion, the results show that the adult human heart expresses SSEAs and that there is a subpopulation of SSEA-4+ CD34- cells that show features of a cardiomyocyte progenitor population.
阶段特异性胚胎抗原(SSEA)表达用于描述胚胎干细胞(ESC)的分化状态。在人类胚胎干细胞中,SSEA - 3和SSEA - 4在未分化细胞中高度表达,分化时下调。SSEA - 4也被描述为包括人类新生儿心脏组织在内的各种组织中成年干细胞的标志物。然而,目前关于SSEAs在人类成年心脏组织中的表达数据很少。我们从接受心脏手术的患者中获取了右心房和左心房活检组织。将这些组织解离,用SSEAs和其他心脏干细胞标志物进行染色,并通过流式细胞术进行分析。直接分离的细胞表达不同水平的SSEA - 1、SSEA - 3和SSEA - 4。SSEA - 1 +群体被确定为污染的造血细胞。另一方面,SSEA - 4 +群体可根据内皮祖细胞标志物CD34进行细分。右心房中的SSEA - 4 + CD34 -群体具有早期(TBX5、NKX2.5)和晚期(TNNT2)心肌细胞标志物的高基因表达。另一方面,SSEA - 4 + CD34 +群体与先前描述的C - kit + CD45 -心脏干细胞重叠。原代单层培养细胞保留了SSEAs的表达,而SSEA - 4 + CD34 -群体中的心肌生成特性丧失。在组织切片中,心肌内外均可识别出SSEA - 4 +细胞。在心肌内,一些SSEA - 4 +细胞共表达心肌生成标志物。总之,结果表明成年人类心脏表达SSEAs,并且存在一个SSEA - 4 + CD34 -细胞亚群,其表现出心肌细胞祖细胞群体的特征。