Distinct Embryonic Origin for Postnatal Dentate Neural Stem Cells

出生后齿状神经干细胞的独特胚胎起源

基本信息

批准号：
8502553
负责人：
SAMUEL JEREMY PLEASURE
金额：
$ 37.08万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8502553
关键词：
Actins Adult Adverse effects Affect Age Alzheimer&apos s Disease Amygdaloid structure Animal Model Animals Anxiety Area Armin Astrocytes Behavior Birth Brain Brain region Breeding Cajal-Retzius cells Cell Lineage Cells Chimera organism Cues Cytoplasmic Granules Data Databases Defect Dendrites Development Disease Dissociation Dorsal Electroporation Embryo Embryonic Development Emigrations Environment Epilepsy Excision Experimental Designs Female Figs - dietary Funding Generations Glass Glial Fibrillary Acidic Protein Goals Grant Hippocampus (Brain)Image Imaging Techniques Immigration Immunofluorescence Immunologic In Situ Hybridization Injection of therapeutic agent Injury Institutes Interneurons Knock-in Mouse Knowledge Label Laboratories Learning Life Ligands Maps Mediating Memory Mental Depression Mental disorders Methodology Methods Modeling Molecular Monitor Mood Disorders Mus Nervous system structure Neurodegenerative Disorders Neuroglia Neurons Oligodendroglia Outcome Pattern Pharmaceutical Preparations Play Primordium Process Production Proliferation Marker Radial Recording of previous events Regulation Relative (related person)Reporter Rodent Role Route Schizophrenia Shapes Siblings Signal Transduction Site Source Staging Stem cells Stimulus Structure Synaptic plasticity Tamoxifen Testing Time Tissues Transplantation Travel Ventricular adult neurogenesis calretinin cohort dentate gyrus design experience granule cell human data in vivo interest mutant nerve injury nerve stem cell neurogenesis novel strategies postnatal pregnant prenatal progenitor programs relating to nervous system repaired research study residence response restoration stem stem cell niche stem cell therapy subventricular zone time use

项目摘要

DESCRIPTION (provided by applicant): The discovery of neural stem/progenitor cells and persistent neurogenesis in restricted brain regions has ignited an unprecedented interest in developing cell restoration therapies, which are designed to repair the malfunctional cells and/or replace the defunct cells in the nervous system in the case of diseases or injuries. Conceivably, we can achieve these either by coaching endogenous stem/progenitor cells for self-repair/self-replenishment, or by transplanting exogenous stem/progenitor cells to differentiate in a defined manner to restore defective or lost cells. However, the successful utilization of neural stem/progenitor cells in either case is contingent on their ability to behave and function in vivo n a biologically meaningful way without causing adverse effects. Many studies in recent years indicate that the fate and behavior of stem/progenitor cells are governed by the local microenvironment, termed the "niche". Therefore, a better understanding of the interactions between the stem/progenitor cells and their niche is a critical step toward effective stem cell therapies. We hope to elucidate the molecular cues mediating interactions between stem/progenitor cells and their niche during development and to encourage use of this knowledge to develop novel approaches for treating neural injuries and neurodegenerative diseases through the following two aims. Aim #1: Examine the contribution of the ventral hippocampal ventricular zone to the production of subgranular NSCs throughout the hippocampus. Aim #2: Characterize the roles of various sources of Shh in SGZ development.

描述（由申请人提供）：神经干/祖细胞和受限大脑区域持续神经发生的发现激发了人们对开发细胞修复疗法的前所未有的兴趣，这些疗法旨在修复功能障碍的细胞和/或替换大脑中的失效细胞。疾病或受伤时的神经系统。可以想象，我们可以通过指导内源干/祖细胞进行自我修复/自我补充，或者通过移植外源干/祖细胞以特定方式分化以恢复缺陷或丢失的细胞来实现这些目标。然而，在任何一种情况下，神经干/祖细胞的成功利用都取决于它们在体内以具有生物学意义的方式表现和发挥功能而不引起不利影响的能力。近年来的许多研究表明，干/祖细胞的命运和行为受局部微环境（称为“生态位”）的控制。因此，更好地了解干/祖细胞及其生态位之间的相互作用是实现有效干细胞治疗的关键一步。我们希望阐明在发育过程中介导干/祖细胞及其生态位之间相互作用的分子线索，并鼓励利用这些知识通过以下两个目标开发治疗神经损伤和神经退行性疾病的新方法。目标#1：检查腹侧海马脑室区对整个海马颗粒下 NSC 产生的贡献。目标#2：描述各种嘘声来源在 SGZ 发展中的作用。