Transcriptomic Entropy to Quantify Maturation of PSC-Derived Cardiomyocytes

项目总结 多能干细胞来源的心肌细胞(PSC-CMS)的不成熟已成为一大挑战 因为它们具有广泛的适用性。出于这个原因，广泛的生物和工程努力正在进行中， 目标是从PSCs中产生成熟的、成人型的CMS。然而，由于缺乏量化指标来衡量 作为PSC-CMS成熟状态的基准，这些努力主要是在特别的基础上进行的，这 PSC-CM的成熟程度和方向尚不清楚。为了解决这个问题，我们开发了一种 基于熵概念的定量度量，支持对实验稳健的交叉比较研究 变异性和物种差异。有了这一发现，这项建议的目的是应用熵分数来确定 分子刺激、组织工程和体内PSC-CM成熟的现状和轨迹 移植，结合功能和结构分析。使用熵得分有望揭示 正在进行的方法的优点和缺点，并告诉我们成熟逮捕和 偏差。因此，拟议的研究将为指导PSC-CM成为 成人CMS以及对PSC-CM在实地成熟过程中取得的进展的定量洞察。

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.