Transcriptomic Entropy to Quantify Maturation of PSC-Derived Cardiomyocytes

项目摘要 多能干细胞衍生的心肌细胞（PSC-CMs）的不成熟性已成为一个主要挑战 其广泛的适用性。出于这个原因，正在进行广泛的生物和工程努力， 目的是从PSC中产生成熟的、成人样的CM。然而，由于缺乏量化指标， 对私营部门支助和协调机制的成熟状况进行基准测试，主要是在临时基础上作出努力， PSC-CM成熟的程度和方向不清楚。为了解决这个问题，我们制定了一个 基于熵概念的定量指标，使交叉比较研究对实验结果具有鲁棒性 变异性和物种差异。有了这一发现，该建议旨在应用熵分数来确定 通过分子刺激、组织工程和体内培养获得PSC-CM成熟的状态和轨迹 移植，结合功能和结构分析。熵值的使用有望揭示 正在进行的方法的优点和缺点，并告知我们成熟停滞的潜在原因， 偏差因此，拟议的研究将提供指导PSC-CM成为 成人CM以及定量的见解朝着PSC-CM成熟在该领域取得的进展。

PROJECT SUMMARY The immaturity of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) has emerged as a major challenge for their broad applicability. For this reason, extensive biological and engineering efforts are underway with the goal to generate mature, adult-like CMs from PSCs. However, owing to the lack of quantitative metrics to benchmark the maturation status of PSC-CMs, the efforts are being made largely on an ad hoc basis, and this leaves the degree and direction of PSC-CM maturation unclear. To address this, we have developed a quantitative metric based on an entropy concept that enables cross-comparison studies robust to experimental variability and species difference. With this finding, this proposal aims to apply entropy score to determine the status and trajectory of PSC-CM maturation achieved by molecular stimulation, tissue engineering, and in vivo transplantation, combined with functional and structural analysis. The use of entropy score is expected to reveal strengths and weaknesses of the ongoing approaches and inform us potential causes of maturation arrest and deviations. Thus, the proposed research will provide mechanistic insights into instructing PSC-CM to become adult CMs as well as quantitative insights into the progress made towards PSC-CM maturation in the field.