Cytokines and lineage choice in hematopoietic precursors

造血前体细胞的细胞因子和谱系选择

基本信息

批准号：
8735141
负责人：
SHERMAN Morton WEISSMAN
金额：
$ 28.97万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-15 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8735141
关键词：
Accounting Adult Aftercare Aliquot Blood Cells CD34 gene CD34+ precursor CSF3 gene Cell Culture Techniques Cell Lineage Cell Therapy Cell physiology Cells DNA Methylation Data Development Emerging Technologies Erythroid Erythropoietin Exposure to Gene Expression Gene Expression Profile Gene Silencing Genes Genetic Transcription Genomics Glycophorin A Goals Grant Granulocyte-Macrophage Colony-Stimulating Factor Harvest Hematopoietic Hematopoietic stem cells Heterogeneity High-Throughput Nucleotide Sequencing Hour Human Individual Instruction Label Length Measurement Measures Methylation Molecular Myelogenous Nature Oligonucleotides Pattern Population Production Repression Role Site Sorting - Cell Movement Specificity Stimulus TFRC gene Testing Thrombopoietin Time Transcript Use of New Techniques cell type cytokine insight mRNA Expression method development peripheral blood precursor cell public health relevance research study response single cell analysis telomere transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): Human CD34+ hematopoietic precursor cells can readily be obtained from the peripheral blood of adults. Treatment of these cells with various cytokine cocktails can induce efficient production of cells differentiated along erythroid, megakaryocytic or myeloid lines. We find that different cytokine cocktails induce rapid and extensive patterns of change in gene expression that are different for different cytokine cocktails. The prominence of these changes suggests that they occur in a large fraction of the CD34+ cells and may modulate the patterns of differentiation of individual cells. The recent development of methods that permit global measurements of mRNA expression, and DNA methylation in single cells make it possible to investigate the role of cytokines in lineage promotion at a level of specificity hitherto unavailable. In the present application we propose to use a combination of single cell genomic scale analyses, and cell tagging and labeling approaches to establish if the same cell can respond differently to different cytokine treatments, and to investigate whether these different responses result in differentiation along alternate lineages. The ultimate goal is to determine the nature of early transcriptional responses to lineage specific cytokines and whether these are instructional as well as permissive for lineage specification.

描述（由申请人提供）：人CD34+造血前体细胞可以很容易地从成年人的外围血液中获得。用各种细胞因子鸡尾酒处理这些细胞可以诱导沿红细胞，巨核细胞或髓样系分化的细胞有效产生。我们发现，不同的细胞因子鸡尾酒会引起基因表达的快速而广泛的变化模式，而不同的细胞因子鸡尾酒不同。这些变化的突出表明它们发生在很大一部分CD34+细胞中，并可能调节单个细胞分化的模式。最近允许全球测量mRNA表达的方法以及单个细胞中的DNA甲基化的发展，使得在迄今无法使用的特异性水平下，可以研究细胞因子在谱系促进中的作用。在本应用中，我们建议将单个细胞基因组尺度分析以及细胞标记和标记方法的组合结合起来，以确定相同细胞是否可以对不同的细胞因子治疗有不同的反应，并研究这些不同的反应是否导致沿替代谱系的分化。最终目标是确定对谱系特定细胞因子的早期转录反应的性质，以及这些反应是否是教学和允许谱系规范的性质。