We present a quantitative co-analysis of RNA abundance and sarcomere organization in single cells and an integrated framework to predict subcellular organization states from gene expression. We used human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes expressing mEGFP-tagged alpha-actinin-2 to develop quantitative image analysis tools for systematic and automated classification of subcellular organization. This captured a wide range of sarcomeric organization states within cell populations that were previously difficult to quantify. We performed RNA FISH targeting genes identified by single cell RNA sequencing to simultaneously assess the relationship between transcript abundance and structural states in single cells. Co-analysis of gene expression and sarcomeric patterns in the same cells revealed biologically meaningful correlations that could be used to predict organizational states. This study establishes a framework for multi-dimensional analysis of single cells to study the relationships between gene expression and subcellular organization and to develop a more nuanced description of cell states.

中文翻译：

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转录组学之外的细胞状态：在hiPSC衍生的心肌细胞中整合结构组织和基因表达

我们目前在单个细胞中的RNA丰度和肌节组织的定量的共同分析和一个集成的框架，以预测从基因表达的亚细胞组织状态。我们使用人类诱导的多能干细胞（hiPSC）衍生的表达mEGFP标签的alpha-actinin-2的心肌细胞来开发定量图像分析工具，用于对亚细胞组织进行系统和自动分类。这捕获了以前难以量化的细胞群内的多种肌节组织状态。我们进行了通过单细胞RNA测序鉴定的RNA FISH靶向基因，以同时评估单细胞中转录物丰度与结构状态之间的关系。对同一细胞中基因表达和肌节模式的共同分析揭示了生物学上有意义的相关性，可用于预测组织状态。这项研究为单个细胞的多维分析建立了一个框架，以研究基因表达与亚细胞组织之间的关系，并发展出对细胞状态更为细致的描述。