Revisiting Cardiac Cellular Composition.
Revisiting Cardiac Cellular Composition.
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DOI：
10.1161/circresaha.115.307778
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发表时间：
2016-02-05
影响因子：
20.1
通讯作者：
Tallquist MD
中科院分区：
文献类型：
--
作者：
Pinto AR;Ilinykh A;Ivey MJ;Kuwabara JT;D'Antoni ML;Debuque R;Chandran A;Wang L;Arora K;Rosenthal NA;Tallquist MD
准确了解心脏的细胞组成对于充分理解在发病过程中发生的变化以及制定组织工程和再生策略至关重要。研究心脏内皮细胞、造血源性细胞和成纤维细胞在小鼠和人心脏中的相对频率。使用遗传工具和细胞标记的组合，我们检查了成年小鼠心脏中最突出的细胞类型的发生。免疫组化显示，心脏非肌细胞中内皮细胞占60%以上，造血来源细胞占5-10%，成纤维细胞占20%以下。精细化的细胞分离方案和改进的流式细胞术方法提供了一种独立的方法来确定非肌细胞的相对丰度。细胞群的高维分析和无监督聚类证实内皮细胞是最丰富的细胞群。有趣的是，成纤维细胞的数量比之前估计的要少，两种常用的成纤维细胞标记，Sca-1和CD90，不能充分代表成纤维细胞的数量。我们还描述了一种替代的成纤维细胞表面标记物，可以更准确地识别常驻心脏成纤维细胞群体。这种关于心脏中不同细胞类型丰度的新观点表明，成纤维细胞构成了一个相对较小的群体。相比之下，内皮细胞构成了非心肌细胞的大部分，并且可能在生理功能和对损伤的反应中发挥比以前认识到的更大的作用。
Accurate knowledge of the cellular composition of the heart is essential to fully understand the changes that occur during pathogenesis and to devise strategies for tissue engineering and regeneration. To examine the relative frequency of cardiac endothelial cells, hematopoietic-derived cells and fibroblasts in the mouse and human heart. Using a combination of genetic tools and cellular markers, we examined the occurrence of the most prominent cell types in the adult mouse heart. Immunohistochemistry revealed that endothelial cells constitute over 60%, hematopoietic-derived cells 5–10%, and fibroblasts under 20% of the non-myocytes in the heart. A refined cell isolation protocol and an improved flow cytometry approach provided an independent means of determining the relative abundance of non-myocytes. High dimensional analysis and unsupervised clustering of cell populations confirmed that endothelial cells are the most abundant cell population. Interestingly, fibroblast numbers are smaller than previously estimated, and two commonly assigned fibroblast markers, Sca-1 and CD90, underrepresent fibroblast numbers. We also describe an alternative fibroblast surface marker that more accurately identifies the resident cardiac fibroblast population. This new perspective on the abundance of different cell types in the heart demonstrates that fibroblasts comprise a relatively minor population. By contrast, endothelial cells constitute the majority of non-cardiomyocytes and are likely to play a greater role in physiologic function and response to injury than previously appreciated.