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Illuminating the chemical biology of stem cell decisions in plant roots

阐明植物根部干细胞决策的化学生物学

基本信息

批准号：
10798493
负责人：
Alexandra Jazz Dickinson
金额：
$ 9.97万
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：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2027-07-31
项目状态：
未结题

项目摘要

Project Summary Small molecules are critical for proper regulation of stem cell behavior in multicellular organisms. Consequently, defects in the biosynthesis, perception, or metabolism of these compounds can cause developmental abnormalities and disease. Despite the critical importance of small molecules, the vast majority of our understanding of their functions is derived from indirect measurements. Typically, studies of small molecule biology are limited to genetic or biochemical approaches that ascribe functional roles to compounds based on the properties of the genes or proteins that interact with these molecules. Alternatively, small molecules are studied using chemical analysis approaches that homogenize bulk tissue and destroy the native context of the signals. High-resolution spatial information is critical in development, where stem cells often comprise a small fraction of the tissue. To enable deeper investigations of chemical regulation of stem cell behavior, my lab will apply technologies capable of directly measuring the localization and activity of small molecules in their native developmental contexts. This work will be done using plant roots, which are a powerful developmental system. Roots store all of their stem cells at the root tip, which generates a developmental gradient that can be examined in a single slice of tissue. My lab will leverage this gradient to investigate the role of small molecules in stem cell decisions. We will map the developmental chemistry of plant roots using mass spectrometry imaging and visualize small molecule interactions with proteins using a synthetic fluorogenic reporter. Metabolite-driven developmental mechanisms will be explored in depth by investigating citrate and retinaldehyde, two highly conserved metabolites with novel roles in root stem cell divisions and identity. This research will generate: 1) high-spatial resolution atlases detailing the chemical profiles of stem cell decisions, from regeneration to differentiation 2) novel insight into pathways that promote proliferation in stress-resilient stem cell subpopulations and 3) elucidation of dynamic metabolite-driven signaling pathways that regulate stem cell patterning. Our preliminary results suggest that there are many small molecules with important developmental roles that await discovery. Conducting research at the intersection of chemistry and developmental biology will provide mechanistic insight into stem cell decisions that would not be possible using a single-disciplinary approach. Accordingly, this work will enrich our understanding of the conserved and divergent principles that govern stem cell patterning, maintenance, divisions, and fate acquisition. Project Summary/Abstract Page 6

项目摘要小分子对于正确调节多细胞生物中的干细胞行为至关重要。因此，委员会认为，这些化合物的生物合成、感知或代谢缺陷可引起发育障碍，异常和疾病。尽管小分子至关重要，但我们绝大多数人对它们的功能的理解来自间接测量。通常，小分子的研究生物学仅限于遗传或生物化学方法，这些方法将功能作用归于基于以下的化合物：与这些分子相互作用的基因或蛋白质的特性。或者，小分子是研究使用化学分析方法，均质化散装组织和破坏的原生环境，信号.高分辨率空间信息在发育中至关重要，其中干细胞通常包含一个小的组织的一部分。为了更深入地研究干细胞行为的化学调控，我的实验室将应用能够直接测量小分子的定位和活性的技术，他们的本土发展背景。这项工作将使用植物的根，这是一个强大的发展体系根将所有的干细胞储存在根尖，可以在单个组织切片中检查的梯度。我的实验室将利用这个梯度来研究小分子在干细胞决策中的作用。我们将绘制植物根系的发育化学图，使用合成荧光光谱成像和可视化小分子与蛋白质的相互作用，记者.代谢驱动的发育机制将通过研究柠檬酸和视黄醛，两种高度保守的代谢产物，在根干细胞分裂和身份中具有新的作用。这研究将产生：1）详细描述干细胞决定的化学概况的高空间分辨率地图集，从再生到分化2）对促进应激适应性细胞增殖的途径的新见解干细胞亚群和3）阐明调节干细胞的动态代谢物驱动的信号传导途径细胞模式我们的初步结果表明，有许多小分子具有重要的有待发现的发展角色。在化学和生物学的交叉点进行研究发育生物学将提供对干细胞决定的机制性见解，这是使用单一学科的方法。因此，这项工作将丰富我们对保守和支配干细胞模式、维持、分裂和命运获得的不同原则。项目摘要/摘要第6页