NSF EAGER: A cross-kingdom comparison of single cell transcriptomes

NSF EAGER：单细胞转录组的跨界比较

• 批准号: 1833182
• 负责人: David Jackson
• 金额: $ 29.94万
• 依托单位: Cold Spring Harbor Laboratory
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1833182&HistoricalAwards=false
• 关键词: NSF; EAGER; cross; kingdom; comparison

Cells are the building blocks of all living organisms and different cell types within an organism are defined by which of their genes they express. However, the precise gene expression profiles that define specific cell types are largely unknown. In addition, it is not known how cells come to express the set of genes that define one cell type versus another or whether the rules that specify cell types differ between plants and animals. This last question is especially interesting because being multicellular evolved independently in these two different kingdoms. The project will address these important questions by sequencing and analyzing mRNA from individual maize cells of different types, making these sequences and their methods and analytical procedures available to the wider plant research community. The project will also contribute to outreach and education by training undergraduate and high school students in genomics and computational biology as part of the Cold Spring Harbor Laboratory Undergraduate Research Program, which has a focus in quantitative biology, as well as the CSHL Partners For The Future Program, both of which train members of groups underrepresented in science. Students from each of these programs will be engaged in this project in both wet lab experiments and in bioinformatics and validation experiments, providing cross-disciplinary training in developmental biology and computational biology. Living organisms develop and function by complex interactions between different specialized cell types. Using an optimized protocol to protoplast developing maize inflorescences, this team will isolate hundreds of thousands of single cells rapidly from different regions of this developing organ. The project will apply expertise in cell biology, genomics and single cell gene expression analysis to identify cell specific expression signatures in maize and to ask how cell type specification compares between plants and animals. A transformative new technology, single cell RNA sequencing (scRNA-seq), offers for the first time the opportunity to profile single plant cells and understand plant development at a fundamentally new level. This method has the power to understand cell type specific networks, to understand transcriptional heterogeneity within cell types and to identify novel regulators of cell fate. The project will test different scRNA-seq technologies and develop informatics tools that can be widely adopted by the plant community, and will be transformative in giving unique insights into single cell transcriptomes across different kingdoms of life. Therefore, this project has the potential to uncover the rules by which cell types are specified across kingdom wide scales. Data generated in this project will be openly available for reanalysis and integration with other datasets. The project will also develop and adapt single cell analysis methods that will be broadly applicable for the plant community.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

细胞是所有生物体的基础，并且在生物体中的不同细胞类型是由它们表达的哪个基因定义的。但是，定义特定细胞类型的精确基因表达谱在很大程度上未知。此外，尚不清楚细胞如何表达定义一种细胞类型与另一种细胞类型的基因集，或者指定细胞类型的规则在植物和动物之间是否有所不同。最后一个问题特别有趣，因为多细胞在这两个不同的王国中独立发展。该项目将通过对不同类型的各个玉米细胞的测序和分析mRNA来解决这些重要问题，从而使这些序列及其方法和分析程序可供更广泛的植物研究社区使用。 该项目还将通过培训基因组学和计算生物学的培训本科生和高中学生为宣传和教育做出贡献，这是Cold Spring Harbour实验室本科研究计划的一部分，该计划专注于定量生物学，以及未来计划的CSHL合作伙伴，这两者都是科学领域不足的群体成员。来自每个计划的学生将在湿实验室实验和生物信息学和验证实验中参与该项目，从而提供发育生物学和计算生物学的跨学科培训。生物体通过不同专业细胞类型之间的复杂相互作用而发展和发挥作用。使用优化的方案来开发玉米花序，该团队将迅速将数十万个单个单元与该发育器官的不同区域隔离开来。该项目将在细胞生物学，基因组学和单细胞基因表达分析中应用专业知识，以识别玉米中细胞特异性表达特征的特异性特异性特征，并询问细胞类型规范如何比较植物与动物之间的比较。一种变革性的新技术，即单细胞RNA测序（SCRNA-SEQ），它首次提供了介绍单个植物细胞并了解植物开发的机会，并从根本上开始了解植物的发育。该方法有能力了解细胞类型特定网络，了解细胞类型中的转录异质性并识别细胞命运的新调节剂。该项目将测试不同的SCRNA-SEQ技术，并开发可以被植物社区广泛采用的信息学工具，并将具有变革性的方式，以对生活的不同王国的单细胞转录组进行独特的见解。因此，该项目有可能揭示跨国范围内指定细胞类型的规则。该项目中生成的数据将公开用于重新分析和与其他数据集集成。该项目还将开发和调整将广泛适用于植物社区的单细胞分析方法。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛的影响评估标准通过评估来支持的。