Schwann Cell Reprogramming after Nerve Injury

神经损伤后雪旺细胞重编程

基本信息

  • 批准号:
    10735147
  • 负责人:
  • 金额:
    $ 54.18万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-06-01 至 2028-05-31
  • 项目状态:
    未结题

项目摘要

Abstract Myelination of axons in the nervous system is critical for not only conduction of action potentials, but also for providing tropic support to ensure long term survival of neurons in both the central and peripheral nervous systems. Myelin disorders are a major cause of neurological disease, and can be caused by genetic disorders, infectious disease, and inflammation. The peripheral nervous system has substantial plasticity in being able to regenerate after nerve injury, and critical transcription factors and their target gene networks have begun to be elucidated. Schwann cell reprogramming to a new differentiated state is a critical and rate limiting factor in peripheral nerve regeneration, particularly when regeneration is impaired as a function of aging/chronic denervation. Therefore, understanding the pathways that control gene expression reprogramming will provide insight into means by which remyelination after nerve injury can be accelerated. The long term objective of our laboratory is to elucidate an integrated mechanism of Schwann cell reprogramming after nerve injury based on critical transcriptional and epigenomic switches. We have found that many critical injury genes are associated with polycomb-associated histone modifications (H3K27me3 and H2AK119ub) prior to injury, and this proposal focuses on testing how reversal of the polycomb pathway is required for Schwann cell responses to peripheral nerve injury. We have also found an expected role of polycomb eraser proteins in myelin homeostasis. Using a variety of techniques established in our laboratory, we will test for the first time the involvement of modulating PRC1 pathway in nerve injury responses. In addition, our work has highlighted mechanisms by which Sonic Hedgehog is activated in repair Schwann cells, and we will employ novel mouse resources to elucidate the mechanisms and role of Sonic Hedgehog signaling in injured peripheral nerve.
摘要 神经系统中轴突的髓鞘形成不仅对神经活动的传导至关重要 电位,但也提供趋向性支持,以确保神经元的长期存活 中枢和外周神经系统。髓鞘疾病是导致 神经性疾病,可由遗传疾病、传染病和 发炎。外周神经系统有很大的可塑性,能够 神经损伤后再生与关键转录因子及其靶基因网络 已经开始被阐明。雪旺细胞重新编程到新的分化状态是一种 周围神经再生中的关键和速度限制因素,特别是再生时 由于衰老/慢性去神经功能而受损。因此,理解这些路径 控制基因表达重新编程将提供对以下方式的洞察 神经损伤后的髓鞘再生可以加速。 我们实验室的长期目标是阐明一种完整的 神经损伤后雪旺细胞基于关键转录和转录因子的重编程 表观基因组开关。我们已经发现许多关键的伤害基因与 损伤前多梳相关的组蛋白修饰(H3K27me3和H2AK119ub),以及 这项建议的重点是测试如何逆转多梳状通路 雪旺细胞对周围神经损伤的反应。我们还发现了一个预期的角色 髓鞘动态平衡中的多梳橡皮擦蛋白。中建立的各种技术 我们的实验室,我们将首次测试参与调节Prc1途径在 神经损伤反应。此外,我们的工作突出了Sonic通过 Hedgehog在修复雪旺细胞中被激活,我们将利用新的小鼠资源来 阐明Sonic Hedgehog信号在周围神经损伤中的作用机制。

项目成果

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Rajeshwar B Awatramani其他文献

Rajeshwar B Awatramani的其他文献

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{{ truncateString('Rajeshwar B Awatramani', 18)}}的其他基金

Developmental underpinnings of substantia nigra vulnerability
黑质脆弱性的发育基础
  • 批准号:
    10322048
  • 财政年份:
    2021
  • 资助金额:
    $ 54.18万
  • 项目类别:
Developmental underpinnings of substantia nigra vulnerability
黑质脆弱性的发育基础
  • 批准号:
    10558560
  • 财政年份:
    2021
  • 资助金额:
    $ 54.18万
  • 项目类别:
Genetic, Molecular and Anatomical Characterization of VTA Cell Types Involved in Pain and Addiction
与疼痛和成瘾相关的 VTA 细胞类型的遗传、分子和解剖学特征
  • 批准号:
    10440297
  • 财政年份:
    2018
  • 资助金额:
    $ 54.18万
  • 项目类别:
Genetic, Molecular and Anatomical Characterization of VTA Cell Types Involved in Pain and Addiction
与疼痛和成瘾相关的 VTA 细胞类型的遗传、分子和解剖学特征
  • 批准号:
    10198888
  • 财政年份:
    2018
  • 资助金额:
    $ 54.18万
  • 项目类别:
Rational derivation of DA neuron subtypes from iPS cells for improved modelling of Parkinson's disease
从 iPS 细胞中合理推导 DA 神经元亚型以改进帕金森病模型
  • 批准号:
    9886284
  • 财政年份:
    2016
  • 资助金额:
    $ 54.18万
  • 项目类别:
Rational derivation of DA neuron subtypes from iPS cells for improved modelling of Parkinson's disease
从 iPS 细胞中合理推导 DA 神经元亚型以改进帕金森病模型
  • 批准号:
    9082946
  • 财政年份:
    2016
  • 资助金额:
    $ 54.18万
  • 项目类别:
Genetic tools to study CNS development and function
研究中枢神经系统发育和功能的遗传工具
  • 批准号:
    9036059
  • 财政年份:
    2015
  • 资助金额:
    $ 54.18万
  • 项目类别:
The developmental basis of dopaminergic neuron diversity
多巴胺能神经元多样性的发育基础
  • 批准号:
    8386303
  • 财政年份:
    2012
  • 资助金额:
    $ 54.18万
  • 项目类别:
The developmental basis of dopaminergic neuron diversity
多巴胺能神经元多样性的发育基础
  • 批准号:
    8472547
  • 财政年份:
    2012
  • 资助金额:
    $ 54.18万
  • 项目类别:
The role of microRNAs in Schwann cell development and disease
microRNA 在雪旺细胞发育和疾病中的作用
  • 批准号:
    7949398
  • 财政年份:
    2010
  • 资助金额:
    $ 54.18万
  • 项目类别:

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大脑动作电位的快速高分辨率深度光声断层扫描
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轴突动作电位的新调节机制
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