A model of repair: intercellular signaling and self-organization in plant regeneration

修复模型：植物再生中的细胞间信号传导和自组织

• 批准号: 10565877
• 负责人: Kenneth David Birnbaum
• 金额: $ 38.56万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-16 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10565877
• 关键词: Address; Adult; Amino Acids; Body part; Cell Communication; Cell Reprogramming; Cells; Chemistry; Communication; Complex; Development; Distant; Embryo; Excision; Fibrinogen; Goals; Health; Human; Imaging Techniques; Injury; Label; Mass Spectrum Analysis; Mediating; Medical; Methods; Modeling; Movement; National Institute of General Medical Sciences; Natural regeneration; Organ; Organ Model; Organogenesis; Plants; Postembryonic; Process; Proteins; Research; Role; Signal Transduction; System; Techniques; Testing; Tissues; Work; adult stem cell; cell type; design; new technology; novel strategies; organ regeneration; organ repair; programs; reconstruction; repair model; self organization; single-cell RNA sequencing; stem cell niche; tool; transcription factor; transcriptomics

PROJECT SUMMARY Plants have exceptional capacity to regenerate adult body parts after injury, providing an excellent conceptual model for organ replacement. They can even rapidly reform their adult stem cell niches after complete excision. My lab has pioneered new systems and techniques to study plant regeneration. We developed methods for tracking cell identity of reprogramming cells using transcriptomic and live imaging techniques during regeneration. In connection with this work, I have led efforts to introduce new technologies like single-cell RNA-seq into plant research. Using these and other techniques developed under NIGMS R01GM078279, we found that regenerating roots appear to recapitulate embryonic programs during organ regeneration. The work has led to us to propose models of how this highly self-organizing system orchestrates the regeneration of an entire organ and its stem cell niche. However, while new tools like in single-cell RNA-seq provide powerful approaches to dissect developmental programs cell-by-cell, they are largely silent on the role of cell-cell communication in mediating tissue assembly. Hence, our current efforts are focused on developing new approaches to address this gap. In one proposed system, we inducibly block symplastic (direct) communication channels in a cell type-specific manner and use single- cell RNA-seq to test the consequences on neighboring and distant tissues during normal post-embryonic organogenesis and regeneration (Block-Seq). This is akin to observing the consequences of signaling from one cell to all its neighbors but not the signals themselves. One common mode of signaling in plants is the protein-level movement of transcription factors from one cell to its neighbors. To track protein movement comprehensively, we are developing a click chemistry approach to incorporate labeled amino acids in specific cell types followed by capture and mass spectrometry of the mobile proteins in neighboring cell types (the Mobilome). This approach is designed to reveal many of the signals that plant cells use to organize development. Overall, these approaches are motivated by a basic question that underpins a medically relevant question: how do positional signals generate a set of rules that allow the flawless reconstruction of organs in regeneration?

项目摘要 植物在受伤后具有出色的能力，可再生成人身体部位，提供出色的 器官更换的概念模型。他们甚至可以在 完整切除。我的实验室已经开创了研究植物再生的新系统和技术。我们 开发的方法用于使用转录组和实时成像跟踪重编程单元的细胞身份 再生过程中的技术。关于这项工作，我领导了介绍新的努力 像单细胞RNA-Seq这样的技术进入植物研究。使用这些技术和其他技术 根据NIGMS R01GM078279，我们发现再生根似乎可以概括胚胎程序 在器官再生期间。这项工作使我们提出了这种高度自组织的模型 系统策划了整个器官及其干细胞生态位的再生。但是，新工具 像单细胞RNA-seq一样，提供了强大的方法来剖析开发程序的单元格， 他们在很大程度上对细胞 - 细胞通信在介导组织组装中的作用保持沉默。因此，我们的 当前的努力集中在开发新方法以解决这一差距。在一个提议的系统中，我们 以细胞类型特异性的方式诱导嵌段构型（直接）通信通道，并使用单一 细胞RNA-seq在正常胚胎后测试对邻近和遥远组织的后果 器官发生和再生（块序列）。这类似于观察信号的后果 一个邻居一个牢房，但不是信号本身。植物中一种常见的信号传导方式是 转录因子从一个细胞到其邻居的蛋白质级运动。跟踪蛋白质运动 全面地，我们正在开发一种点击化学方法，以将标记的氨基酸纳入 特定的细胞类型，然后在相邻细胞中捕获移动蛋白的质谱和质谱 类型（动员）。这种方法旨在揭示植物细胞使用的许多信号 组织发展。总体而言，这些方法是由一个基础的基本问题激励的 与医学相关的问题：位置信号如何产生一组允许完美无瑕的规则 重建器官的再生？