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Defining the cause and consequence of aging-specific platelet specification from hematopoietic stem cells

定义造血干细胞衰老特异性血小板规格的原因和后果

基本信息

批准号：
10621901
负责人：
CAMILLA FORSBERG
金额：
$ 54.69万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA CRUZ
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10621901
关键词：
Activities of Daily Living Affect Age Aging B-Lymphocytes Biological Assay Blood Blood Platelets Blood coagulation Cardiovascular Diseases Cell Transplantation Cells Cues Disease Elderly Erythrocytes Event Exposure to FLT3 gene Generations Genes Goals Half-Life Health Hematopoietic Hematopoietic Stem Cell Specification Hematopoietic Stem Cell Transplantation Hematopoietic System Hematopoietic stem cells Hemorrhage Hemostatic function Immune Immunologic Stimulation Individual Inflammatory Knowledge Life Longevity Mediating Mediator Megakaryocytes Megakaryocytopoieses Molecular Molecular Analysis Morbidity - disease rate Mus Ontology Outcome Parabiosis Pathway interactions Physiology Plague Platelet Activation Platelet Count measurement Platelet aggregation Play Population Process Production Regulation Resolution Risk Role Serum Specific qualifier value Stroke System T-Lymphocyte Testing Thrombocytopenia Thrombosis Tomatoes Transplantation age related aged aging population experimental study immunoregulation improved inflammatory milieu interleukin-21 mouse model novel platelet function prevent progenitor self-renewal single-cell RNA sequencing stem stem cells thrombocytosis thrombotic transcriptome young adult

项目摘要

PROJECT SUMMARY/ABSTRACT Our goal is to understand platelet (Plt) production and function upon aging. Plts play essential roles in hemostasis, the process of preventing bleeding, and also participate in immune regulation. Aging is associated with a dramatic increase in platelet-related disorders, including alterations in Plt numbers (thrombocytosis or thrombocytopenia) and in Plt activity. Plts have a very short half-life and are continually produced by hematopoietic stem cells (HSCs). We have discovered that the differentiation pathways of Plt production are different in young and old mice. Here, we propose to investigate the molecular and cellular mechanisms behind the aging-specific differentiation path, and the consequences for Plt function and aging physiology. We hypothesize that the aging-specific Plt pathway contributes to the dramatically increased risk for Plt-related disorders in the elderly. Our discovery of a new, age-specific differentiation pathway provides a unique opportunity for novel discoveries towards mitigating Plt-related disorders, including thrombosis and cardiovascular disease, in the elderly.

项目总结/摘要我们的目标是了解血小板（Plt）的生产和功能老化。Plts在以下方面发挥重要作用：止血、防止出血的过程，还参与免疫调节。衰老与血小板相关疾病的急剧增加，包括血小板数量的改变（血小板增多或血小板减少症）和Plt活性。PLT的半衰期很短，造血干细胞（HSC）。我们已经发现Plt产生的分化途径是在年轻和年老的老鼠身上是不同的。在这里，我们建议调查背后的分子和细胞机制，衰老特异性分化途径，以及Plt功能和衰老生理学的后果。我们假设衰老特异性Plt途径导致Plt相关风险显着增加老年人的疾病。我们发现了一种新的年龄特异性分化途径，缓解Plt相关疾病（包括血栓形成和老年人的心血管疾病