Molecular Mechanisms of Stem Cell Homeostasis in Arabidopsis

拟南芥干细胞稳态的分子机制

• 批准号: 10642908
• 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/10642908
• 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; Computer Models; Cytokinins; Defect; Diabetes Mellitus; Disease; Exclusion; Family; Functional disorder; Future; Genes; Genetic; Genetic Transcription; Goals; Health; Heart Diseases; High-Throughput RNA Sequencing; Homeostasis; Hormones; Human; Image Analysis; Immobilization; In Vitro; Knowledge; Lateral; Lead; Meristem; Metabolism; Modeling; Molecular; Molecular Genetics; Nerve Degeneration; Organ; Organism; Organogenesis; Pathway interactions; Plants; Play; Pluripotent Stem Cells; Proliferating; Proteins; Regulation; Reporter; Repression; Research; Role; Series; Side; Signal Transduction; Surface; System; Testing; Time; Undifferentiated; Work; cell behavior; cell fate specification; cell growth; cell type; confocal imaging; daughter cell; experimental study; fluorescence imaging; gene function; genetic approach; genetic resource; human disease; imaging approach; in silico; in vivo; live cell imaging; mutant; organ growth; peptide hormone; plant growth/development; self-renewal; stem cell fate specification; stem cell function; stem cell homeostasis; stem cell niche; stem cell population; stem cell proliferation; 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.

摘要 在包括动物、植物和人类在内的多细胞生物体中，干细胞在 保持自身未分化但持续分裂以维持器官发育和身体 队形。干细胞功能缺陷会导致器官发育异常和疾病。在另一边， 解开干细胞的行为和调控可以提供有效的基于细胞的治疗，包括组织 再生治疗人类疾病，如神经退行性变、糖尿病和心脏病。到目前为止， 控制干细胞微环境的启动、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。 以拟南芥顶端分生组织(SAM)为模型系统。因为体内未分化的干细胞 拟南芥的SAM在表面和附近，活的SAM在实验过程中可以保持固着， 非侵入性的延时活体成像方法在拟南芥中尤其有效，以跟踪 每一种干细胞及其衍生物，并量化体内的细胞动力学。此外，中国丰富的遗传资源 拟南芥允许我们通过使用现有的突变体阵列来定量分析基因功能 改变了SAM大小和干细胞数量。使用该系统，通过在体内结合延时 共聚焦成像、基因功能的瞬时和稳定扰动、体外生化和硅胶研究 量化和建模方法，我们的目标是揭示一小群关键字 从干细胞中排除但决定干细胞的特性和活性的转录调节因子 SAM中的细胞。我们的工作不仅将定义尚不存在的分子连接和细胞间通讯 分化和未分化细胞之间的关系，但也阐明了细胞非 干细胞内稳态控制中的自主现象。