Midwestern Progenitor Cell Consortium

中西部祖细胞联盟

• 批准号: 8494683
• 负责人: Daniel J. Garry
• 金额: $ 106.68万
• 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 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8494683
• 关键词: Address; Adopted; Blood; Blood Vessels; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cells; Cellular biology; Chronic Disease; Clinical; Cues; Embryo; Emerging Technologies; Genetic 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）： 血液和心血管疾病既常见又致命。这些疾病是长期的，令人衰弱的，因此需要新颖的疗法。血液和心血管程序具有许多重叠的特征，因为这两者都是侧板中胚层衍生物，并且都通过高度相交的转录因子，信号级联和细胞外提示的网络来凝聚。在我们机构进行的项目将定义网络中的关键调节节点，这些节点促进干细胞和祖细胞采用造血和心血管细胞命运，以改善临床选择。我们将破译细胞内，细胞外和旁分泌因子，这些因子促进茎/祖细胞的规格以及对心脏，血管和造血限制谱系的分化。在这些项目中，我们将利用一系列工具和新兴技术，包括转基因鼠标模型，基因设计的胚胎和诱导的多能干细胞，克隆心脏祖细胞群体，脱细胞的心脏，心脏和最新的最先进的高分辨率/高分辨率成像/光谱技术将在我们的研究中与我们的研究，并在我们的研究中建立了这些研究。祖细胞生物学研究联盟。该提案的总体目标是机械地破译细胞内和细胞外网络，这些网络控制干细胞对心血管和造血谱系的规范和分化。为了解决这一总体目标，我们将追求以下项目：项目＃1：定义在hESC和HIPSC衍生的中胚层中指定造血计划的转录机制。项目＃2：定义在MES/EBS，HESC，HIPSC和心脏祖细胞中指定心血管程序的转录和信号网络。项目＃3：定义细胞外提示，包括直接心血管分化和功能的细胞基质相互作用。项目＃4：定义从hESC和HIPSC得出的心肌再生的最佳细胞种群。这些协作研究的结果将成为血液疾病和心血管疾病新兴疗法的平台。