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Multi-Omics Approach to Identify Cardiokines in Human iPSC Models

识别人类 iPSC 模型中心肌因子的多组学方法

基本信息

批准号：
10450844
负责人：
Edward Lau
金额：
$ 23.99万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-20 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10450844
关键词：
Address Adopted Biological Assay Biological Process Cardiac Cardiac Myocytes Cardiomyopathies Cardiovascular system Catalogs Cell model Cells Communication Computational Technique Contracts Data Development Dilated Cardiomyopathy Disease Disease Pathway Endothelial Cells Extracellular Space Fibroblasts Foundations Gene Expression Genes Goals Health Heart Heart Diseases Heart failure Human In Vitro Ligands Light Maps Mass Spectrum Analysis Mediating Modeling Multiomic Data Muscle Cells Natriuretic Peptides Normal Cell Nucleic Acids Pattern Phase Physiological Play Process Proteins Proteomics Research Role Signal Transduction Work causal variant cell type experimental study extracellular induced pluripotent stem cell induced pluripotent stem cell derived cardiomyocytes interest multiple omics novel protein function receptor single cell sequencing single-cell RNA sequencing stem cell model

项目摘要

The human heart actively releases protein messengers into the extracellular space. Recent work suggests that these secreted proteins, termed cardiokines, can mediate cellular crosstalk that plays important roles in the development of cardiomyopathies and heart failure. Although several classical cardiokines such as the natriuretic peptides have been extensively characterized, there have been few efforts to systematically catalog the proteins secreted by human cardiac cells. Using proteomics and human induced pluripotent stem cell (hiPSC) models, we recently created a draft map of the human cardiac secretome through identifying and contrasting secreted molecules from hiPSC-derived cardiomyocytes, cardiac fibroblasts, and endothelial cells. The results revealed a surprisingly large number of candidate cardiokines released from each cell type including many secreted proteins with uncharacterized function in the cardiovascular system. Moreover, we found broad changes in the secretome patterns of cardiomyocytes carrying dilated cardiomyopathy causal variants over normal cells. Building on these findings, our aims in the R00 phase are now to (i): identify cardiomyocyte secreted proteins that function in fibroblast crosstalk and predict the biological processes they regulate; and (ii) prioritize disease-relevant cardiokines and validate their effects on recipient fibroblast gene expression. To achieve these aims, we will employ a combination of computational, single-cell sequencing, and proteomics strategies building on hiPSC models as our foundation. If successful, the proposed research has the potential to uncover a number of novel secreted proteins and their function in human cardiac cells, and shed light on the role of cellular communications in the development and progression of cardiomyopathies.

人类心脏会主动向细胞外空间释放蛋白质信使。最近的研究表明

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Defining the Roles of Cardiokines in Human Aging and Age-Associated Diseases.

DOI：
10.3389/fragi.2022.884321
发表时间：
2022
期刊：
FRONTIERS IN AGING
影响因子：
0
作者：
Srivastava, Himangi;Pozzoli, Marina;Lau, Edward
通讯作者：
Lau, Edward

Harmonizing Labeling and Analytical Strategies to Obtain Protein Turnover Rates in Intact Adult Animals.

DOI：
10.1016/j.mcpro.2022.100252
发表时间：
2022-07
期刊：
MOLECULAR & CELLULAR PROTEOMICS
影响因子：
7
作者：
Hammond, Dean E.;Simpson, Deborah M.;Franco, Catarina;Muelas, Marina Wright;Waters, John;Ludwig, R. W.;Prescott, Mark C.;Hurst, Jane L.;Beynon, Robert J.;Lau, Edward
通讯作者：
Lau, Edward