Molecular Mechanisms of Stem Cell Homeostasis in Arabidopsis

拟南芥干细胞稳态的分子机制

• 批准号: 10278380
• 负责人: Yun Zhou
• 金额: $ 31.04万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10278380
• 关键词: 3-Dimensional; Adenine; Animals; Apical; Arabidopsis; Biochemistry; Biological Models; Cell Communication; Cell Count; Cell Cycle; Cell Differentiation process; Cell Therapy; Cell division; Cell physiology; Cells; Communication; Cytokinins; Daughter; Defect; Diabetes Mellitus; Disease; Equilibrium; Exclusion; Family; Functional disorder; Future; Gene Proteins; Genes; Genetic; Genetic Transcription; Goals; Health; Heart Diseases; High-Throughput RNA Sequencing; Homeostasis; Hormones; Human; Image Analysis; In Vitro; Knowledge; Lateral; Lead; Meristem; Metabolism; Modeling; Molecular; Molecular Genetics; Nerve Degeneration; Organ; Organism; Organogenesis; Pathway interactions; Plants; Play; Pluripotent Stem Cells; Regulation; Reporter; Repression; Research; Role; Series; Side; Signal Transduction; Specific qualifier value; Surface; System; Testing; Time; Undifferentiated; Work; base; cell behavior; cell fate specification; cell growth; cell type; confocal imaging; experimental study; fluorescence imaging; gene function; genetic approach; genetic resource; human disease; human stem cells; imaging approach; in silico; in vivo; live cell imaging; mutant; organ growth; peptide hormone; plant growth/development; self-renewal; stem cell function; stem cell homeostasis; stem cell population; stem cells; tissue regeneration

ABSTRACT In multicellular organisms including animals, plants and human beings, stem cells play conserved roles in maintaining themselves undifferentiated but continuously dividing to sustain organ development and body formation. Defects in stem cell function lead to abnormal organ development and diseases. On the other side, unraveling stem cell behavior and regulation can provide effective cell-based therapies including tissue regeneration for human diseases such as neurodegeneration, diabetes, and heart disease. To date, the regulatory mechanisms controlling the initiation, proliferation and termination of stem cell niches are still not fully understood. Here, we propose to determine the cellular and molecular basis underlying stem cell homeostasis using the Arabidopsis shoot apical meristem (SAM) as a model system. Because undifferentiated stem cells in Arabidopsis SAMs are at and near the surface and the living SAMs can maintain sessile during experiments, non-invasive time-lapse live imaging approaches are particularly effective in Arabidopsis, to follow the fate of each stem cell and their derivatives and to quantify cell dynamics in vivo. In addition, great genetic resources in Arabidopsis allow us to quantitatively dissect gene function through using an existing array of mutants with changed SAM sizes and stem cell numbers. Using this system, through a combination of in vivo time-lapse confocal imaging, transient and stable perturbations of gene function, in vitro biochemistry and in silico quantification and modeling approaches, we aim to uncover mechanisms by which a small group of key transcriptional regulators that are excluded from stem cells but determine the identity and activity of the stem cells in the SAMs. Our work will not only define the yet missing molecular linkage and cell-cell communication between differentiated and undifferentiated cells, but also elucidate a regulatory network underlying a cell non- autonomous phenomenon in control of stem cell homeostasis.

抽象的 在包括动物、植物和人类在内的多细胞生物体中，干细胞在以下方面发挥着保守的作用： 保持自身未分化但不断分裂以维持器官发育和身体 形成。干细胞功能缺陷会导致器官发育异常和疾病。另一边， 揭示干细胞的行为和调节可以提供有效的基于细胞的疗法，包括组织疗法 神经退行性疾病、糖尿病和心脏病等人类疾病的再生。迄今为止， 控制干细胞巢的起始、增殖和终止的调控机制仍然不完全 明白了。在这里，我们建议确定干细胞稳态的细胞和分子基础 使用拟南芥芽顶端分生组织（SAM）作为模型系统。因为未分化的干细胞 拟南芥 SAM 位于地表及其附近，活的 SAM 可以在实验过程中保持固着， 非侵入性延时实时成像方法在拟南芥中特别有效，可以追踪拟南芥的命运 每个干细胞及其衍生物并量化体内细胞动态。此外，我国还拥有丰富的遗传资源。 拟南芥允许我们通过使用现有的突变体阵列来定量剖析基因功能 改变了 SAM 大小和干细胞数量。使用该系统，通过结合体内延时 共聚焦成像、基因功能的瞬时和稳定扰动、体外生物化学和计算机模拟 量化和建模方法，我们的目标是揭示一小群关键的机制 转录调节因子被排除在干细胞之外，但决定干细胞的身份和活性 SAM 中的细胞。我们的工作不仅将定义尚缺失的分子联系和细胞间通讯 分化和未分化细胞之间的关系，而且还阐明了细胞非分化背后的调控网络 控制干细胞稳态的自主现象。