Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
McKusick - Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Cardiovasc Pathol. 2018 May-Jun;34:50-57. doi: 10.1016/j.carpath.2018.03.002. Epub 2018 Mar 24.
Skeletal myocytes have well-established fast and slow twitch fibers with unique gene and protein specific expression patterns. By immunohistochemical staining, these show a mosaic pattern across myocytes. We hypothesized cardiac myocytes may behave similarly where some proteins are differentially expressed between mature cardiomyocytes. We utilized the tool HPASubC on over 52,000 cardiac images of the Human Protein Atlas to identify differential protein expression patterns by immunohistochemistry across the cardiomyocytes. We matched identified proteins to open chromatin and gene expression data. We identified 143 putative proteins with mosaic patterns of expression across the cardiomyocytes. We validated four of these proteins (MYL3, MYL4, PAM, and MYOM1) and demonstrated unique atrial or ventricular patterns of expression for each. Acetylation of histone H3K27 at the promoters of these four genes were consistent with the atrial/ventricular expression patterns. Despite the generally accepted homogeneity of cardiomyocytes, a small subset of proteins varies between cardiomyocytes in a mosaic pattern. This fundamental process has been previously uncharacterized. These changes may inform on different functional and disease-related activities of proteins in individual cardiomyocytes.
骨骼肌肌细胞具有明确的快肌和慢肌纤维，具有独特的基因和蛋白特异性表达模式。通过免疫组织化学染色，这些模式在肌细胞中呈现出镶嵌模式。我们假设心肌细胞可能也有类似的行为，其中一些蛋白在成熟的心肌细胞之间存在差异表达。我们利用 Human Protein Atlas 上超过 52000 张心脏图像的 HPASubC 工具，通过免疫组织化学鉴定心肌细胞中差异表达的蛋白模式。我们将鉴定出的蛋白与开放染色质和基因表达数据进行匹配。我们在心肌细胞中鉴定出了 143 种具有镶嵌表达模式的假定蛋白。我们验证了其中的 4 种蛋白（MYL3、MYL4、PAM 和 MYOM1），并证明了每种蛋白都具有独特的心房或心室表达模式。这 4 个基因启动子处的组蛋白 H3K27 的乙酰化与心房/心室表达模式一致。尽管人们普遍认为心肌细胞是同质的，但一小部分蛋白在镶嵌模式下在心肌细胞之间存在差异。这个基本过程以前没有被描述过。这些变化可能提示个体心肌细胞中蛋白的不同功能和疾病相关活性。
