Midwest Progenitor Cell Consortium

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DESCRIPTION (provided by applicant): The Midwest Progenitor Ciell Consortium is a collaboration between the UW-Madison and the UMN which will serve as a research hub within the NHLBI's Progenitor Cell Biology Consortium. The goal is to develop new strategies to convert human pluripotent stem and somatic cells into hematopoietic stem cells (HSCs) and selfrenewing cardiac progenitor cells through identification of genetic program leading to formation of pre-HSCs and cardiac progenitors and activation of self-renewal program in lineage-restricted cells. Project 1, "The De Novo Generation of Hematopoietic Stem CeUs from Human ES/iPS Cells and Somatic Cells," aims are: Identify the hierarchy of mesodermal progenitors of vascular endothelial and hematopoietic lineages using human ES cell lines with targeted FOXFl, GATA-2, GATA-3, RUNXl, and SCL genes; Determine the most critical molecular events leading to formation of hematopoietic cells and HSCs during embryogenesis in mouse aind human, and following in vitro differentiation of human pluripotent stem cells; Develop technologies for de novo generation of HSCs from human ES/iPS cells and somatic cells. Project 2, "Cardiovascular Progenitors and Cardiomyocytes from Human ES/iPS Cells and Somatic Cells," aims are: Isolate and define human embryonic cardiovascular progenitors and ventricular myocytes derived from pluripotent stem cells; and reprogram human pluripotent stem cells and somatic cells using transcription factors to generate cardiovascular progenitors and ventricular myocytes. Project 3, "Artificial Transcription Factors for Reprogramming/Transdifferentation," aims are: Design ATFs that activate expression of Oct4, Sox2 or Nanog in primary fibroblasts; Perform genome-wide location analysis, CSI and transcriptome analysis to determine gene targets and specificity ofthe designed ATFs; and combine ATFs to induce pluripotency in primary fibroblasts. Project 4, "Rapid In Vitro Generation of Affinity Reagents for Hematopoietic and Cardiovascular Precursors," aims are: Develop methods for rapidly generating aptamers that bind to transmembrane protein targets with high affinity and specificity; Develop methods to accelerate discovery of aptamers with sub nanomolar affinities using high-throughput DNA sequencing technologies; and generate high affinity aptamers for surface markers of cardiovascular and blood precursors.