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Analysis of RNA binding proteins directing hematopoietic stem cell fate

指导造血干细胞命运的RNA结合蛋白分析

基本信息

批准号：
9926912
负责人：
Kristin Hope
金额：
$ 61.29万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9926912
关键词：
Address Aryl Hydrocarbon Receptor Binding Biochemical Biological Assay Bone Marrow Cell physiology Cells Chemicals Clinical Code Complement Complex Coupled Critical Pathways Custom Cytometry Data Set Decision Making Development Disease Engineering Ensure Equilibrium Event Gene Expression Genetic Transcription Genomics Goals Gold Hematopoiesis Hematopoietic Hematopoietic System Hematopoietic stem cells Human Immune System Diseases Immunofluorescence Immunologic In Vitro Informal Social Control Interruption Knock-in Mouse Maintenance Maps Mass Spectrum Analysis Mediating Messenger RNA Methods Molecular Mus Nature Outcome Output Pathway interactions Phenocopy Polyadenylation Population Post-Transcriptional Regulation Process Proteomics Publishing RNA RNA Splicing RNA analysis RNA-Binding Proteins Regulation Regulon Repression Ribonucleoproteins Role System Techniques Technology Testing Tissues Transcript Translational Research Translations Umbilical Cord Blood Work base cell type cofactor crosslinking and immunoprecipitation sequencing design effective therapy gain of function gene repression genetic regulatory protein hematopoietic stem cell differentiation hematopoietic stem cell fate hematopoietic stem cell self-renewal imaging approach in vivo insight interdisciplinary approach leukemia novel novel therapeutics overexpression progenitor regenerative self-renewal stem cell fate stem cells stemness transcriptome

项目摘要

Project Summary RNA binding proteins control the molecular fate of RNA substrates and are often underappreciated regulatory factors in development. In recent work, we identified the RNA binding protein MSI2 in the control of human hematopoietic stem cell self-renewal (Rentas et al, Nature, 2016) and establish RNA binding proteins as key regulators of this process. In this proposal, we aim to functionally characterize using gold-standard in vitro and in vivo assays a novel MSI2-interactor and putative HSC-regulator. We will also utilize a combination of mass spectrometry and cytometry (single-cell) to identify MSI2-interacting RNA binding proteins in primitive hematopoietic cells. We will apply our enhanced CLIP-seq approach to identify RNA substrates of these RBPs and identify critical pathways which we can manipulate to enhance HSC self-renewal or direct HSC fate. We will utilize cutting edge methods like our recently published RNA-targeting Cas9 (Nelles et al, Cell, 2016) to identify novel RBPs and post-transcriptional circuitries essential for HSC function.

项目总结