Midwestern Progenitor Cell Consortium

中西部祖细胞联盟

• 批准号: 7833748
• 负责人: Daniel J. Garry
• 金额: $ 113.25万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7833748
• 关键词: Address; Adopted; Arts; Blood; Blood Vessels; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cells; Cellular biology; Chronic Disease; Clinical; Cues; Embryo; Emerging Technologies; Engineering; Goals; Heart; Hematological Disease; Hematopoietic; Image; Institution; Lateral; Mesoderm; Myocardial; National Heart, Lung, and Blood Institute; Natural regeneration; Population; Research; Resolution; Signal Transduction; Specific qualifier value; Spectrum Analysis; Stem cells; Technology; Transgenic Mice; Universities; Wisconsin; extracellular; human embryonic stem cell; improved; induced pluripotent stem cell; mouse model; novel; paracrine; progenitor; programs; stem; stem cell differentiation; tool; transcription factor

DESCRIPTION (provided by applicant): Blood and cardiovascular diseases are both common and deadly. These diseases are chronic, debilitating and they warrant novel therapies. The blood and cardiovascular programs have a number of overlapping features as both are lateral plate mesodermal derivatives and both are coregulated by highly intersecting networks of transcription factors, signaling cascades and extracellular cues. The projects undertaken at our institution will define the key regulatory nodes in the networks that promote stem cells and progenitor cells to adopt a hematopoietic and cardiovascular cell fate - with an aim toward improving clinical options. We will decipher the intracellular, extracellular and paracrine factors that promote stem/progenitor cell specification and differentiation to cardiac, vascular and hematopoietic restricted lineages. In these projects, we will utilize an array of tools and emerging technologies including transgenic mouse models, genetically engineered embryonic and induced pluripotent stem cells, clonal cardiac progenitor cell populations, the decellularized heart, and state-of-the-art high resolution imaging/spectroscopy technologies, which will facilitate our studies and those of our collaborators at the University of Wisconsin and those associated with the NHLBI Progenitor Cell Biology Research Consortium. The overall goal of this proposal is to mechanistically decipher the intracellular and extracellular networks that govern specification and differentiation of stem cells to the cardiovascular and hematopoietic lineages. To address this overall goal, we will pursue the following projects: Project #1: To define the transcriptional mechanisms that specify the hematopoietic program in hESC- and hiPSC-derived mesoderm. Project #2: To define the transcriptional and signaling networks that specify the cardiovascular program In mES/EBs, hESC, hIPSC, and cardiac progenitors. Project #3: To define the extracellular cues including cell matrix interactions that direct cardiovascular differentiation and function. Project #4: To define the optimal cell populations derived from hESCs and hiPSCs for myocardial regeneration. The results of these collaborative studies will serve as a platform for emerging therapies for blood disorders and cardiovascular disease.

描述（由申请人提供）：