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Transcriptional Control of adult hippocampal neural stem cell homeostasis

成人海马神经干细胞稳态的转录控制

基本信息

批准号：
10201930
负责人：
Amar Sahay
金额：
$ 50.78万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10201930
关键词：
Adult Aging Animals Astrocytes Brain Brain Diseases Cell Count Cell Maintenance Cells Clone Cells Coupled Data Disease Engineering Ensure Equilibrium Exhibits Foundations Genetic Glean Goals Hippocampus (Brain)Image Individual Injury Knock-in Knock-in Mouse Knock-out Knockout Mice Label Maintenance Mediating Molecular Mus Mutation Neuroglia Pattern Photons Physiological Population Process Proteins Protocols documentation Radial Regulation Reporter Signal Transduction Structure Testing Time Tissues Transcriptional Regulation Trees Ventricular Zinc Fingers dentate gyrus granule cell in vivo insight loss of function nerve stem cell neurogenesis neuroregulation overexpression preservation prevent progenitor recruit relating to nervous system response satellite cell self-renewal stem stem cell differentiation stem cell division stem cell homeostasis stem cells transcription factor

项目摘要

Maintenance of somatic tissue functions necessitates stem cells to adaptively respond to physiological signals and differentiate while ensuring self-preservation through regulation of quiescence and self-renewal. Radial glia-like neural stem cells in the dentate gyrus subregion of the adult hippocampus give rise to dentate granule cells and astrocytes, a process referred to as adult hippocampal neurogenesis. Neural stem cells must balance long-term maintenance with demands for differentiation and expansion in response to distinct physiological signals. These fundamental decisions are governed by niche-signals that recruit cell-autonomous factors within adult hippocampal neural stem cells. Although a growing number of studies have begun to identify transcription factors that couple the regulation of adult hippocampal neural stem cell quiescence with asymmetric self-renewal, the identities of transcription factors that couple regulation of quiescence and symmetric self-renewal in the adult hippocampus (or adult brain) are largely not known. Here, we will test the central hypothesis that Kruppel-like factor 9 (Klf9), a zinc finger transcription factor, contributes to long-term maintenance and neural stem cell expansion in the adult hippocampus through regulation of quiescence and symmetric stem cell divisions. Towards this goal, we will build on our extensive preliminary data employing newly engineered conditional Klf9 knock out and mCherry knock-in fusion mice, population and clonal lineage tracing, and longitudinal live 2 photon imaging of individual adult hippocampal neural stem cells in vivo. Execution of the proposed Aims will establish a foundation for understanding how Klf9 levels in neural stem cells balance long-term preservation through regulation of quiescence with rapid mobilization and expansion through control of symmetric self-renewal in the adult brain. Insights gleaned from this proposal may guide strategies to replenish/expand the pool of neural stem cells and restore hippocampal circuit plasticity in different disease states, aging and following injury.

体细胞组织功能的维持需要干细胞做出适应性反应