Transcriptomic Entropy to Quantify Maturation of PSC-Derived Cardiomyocytes

转录组熵量化 PSC 衍生心肌细胞的成熟

基本信息

批准号：
10179233
负责人：
Deok-Ho Kim
金额：
$ 56.98万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10179233
关键词：
Address Adolescent Adult Algorithms Animals Benchmarking Biological Cardiac Myocytes Cells Clinical Trials Data Data Set Development Electric Stimulation Engineering Entropy Gene Expression Gene Expression Profile Generations Genes Genetic Transcription Glucocorticoid Receptor Goals Gold Heart Incubated Libraries Measures Mechanical Stimulation Meta-Analysis Metabolic Methodology Methods Modeling Molecular Mus Output PPAR gamma Perinatal Peroxisome Proliferator-Activated Receptors Pluripotent Stem Cells Preparation Protocols documentation Regulator Genes Research Sorting - Cell Movement Structure Testing Thyroid Hormone Receptor Time Tissue Engineering Tissue-Specific Gene Expression Tissues Transplantation base cardiac tissue engineering fetal heart damage human tissue in vivo insight mature animal multiple datasets novel particle postnatal repaired single-cell RNA sequencing species difference tool transcriptome transcriptomics

项目摘要

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.

项目概要多能干细胞衍生的心肌细胞（PSC-CM）的不成熟已成为一项重大挑战因其广泛的适用性。出于这个原因，广泛的生物和工程工作正在进行中目标是从 PSC 中产生成熟的、类似成人的 CM。但由于缺乏量化指标对 PSC-CM 的成熟状态进行基准测试，这些努力主要是在临时基础上进行的，并且这 PSC-CM 成熟的程度和方向尚不清楚。为了解决这个问题，我们开发了一个基于熵概念的定量度量，使交叉比较研究对实验具有鲁棒性变异性和物种差异。根据这一发现，本提案旨在应用熵分数来确定通过分子刺激、组织工程和体内实现的 PSC-CM 成熟的状态和轨迹移植，结合功能和结构分析。熵分数的使用有望揭示现行方法的优点和缺点，并告诉我们成熟停滞的潜在原因和偏差。因此，拟议的研究将为指导 PSC-CM 成为成人 CM 以及对该领域 PSC-CM 成熟进展的定量见解。