Functional engraftment of stem cell-derived cortical interneurons

干细胞来源的皮质中间神经元的功能植入

基本信息

  • 批准号:
    8618809
  • 负责人:
  • 金额:
    $ 8.8万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-09-20 至 2015-08-31
  • 项目状态:
    已结题

项目摘要

Abstract Cortical interneurons represent a broad class of inhibitory neurons that are essential for controlling brain excitability and coordinating behavior. Disruption of inhibitory circuits has been implicated in a number of brain disorders, including epilepsy, intellectual disability, autism, schizophrenia, and head injury. Recently, advances in mouse and human stem cell research suggest that pluripotent cells can be used to generate enriched populations of cortical neurons and interneurons in vitro. However, few studies have systematically examined how exogenous inhibitory neurons derived from stem cell sources might be used as a cell-therapy to modify neural circuitry in vivo. The overall goal of this K99/R00 application is to determine how cortical interneurons derived from mouse and human induced pluripotent stem cells (iPS cells) functionally incorporate into the postnatal brain. The mentored phase of the award will be conducted at University of California, San Francisco under the guidance of Dr. Scott Baraban and the project will be continuted in my own laboratory after an independent faculty position is secured. In Specific Aims 1 and 2, I will use a promoter-based reporter construct to purify coritcal interneuron precursors generated from iPS cells and characterize their differentiation in vitro (Aim 1) and after transplantation (Aim 2) using a series of anatomical, molecular, and electrophysiological approaches. In Aim 3 (R00 phase), I will determine the connectivity patterns of iPS cell- derived interneurons grafted into the postnatal brain. Understanding how cortical interneurons generated from stem cell sources functionally incorporate into the recipient circuitry will provide new information about their functional plasticity and is a critical step toward translating these findings into new interneuron-based cell therapies. My long term goal is to build an independent dedicated to understanding mechanisms of neural circuit organization and to develop novel stem cell strategies for brain repair and regeneration, particularly for brain disorders associated with interneuron dysfunction. This research will require extensive training in stem cell biology, and UCSF is an outstanding institution to complete the mentored phase of this application, primarily due to the rich community of prominent neuroscientists and clinicians performing neural stem cell research and the pioneering role of UCSF in the stem cell field. In addition to Dr. Baraban's outstanding mentorship, I have assembled a team of internationally recognized scientists who will provide me with hands- on technical training, formal coursework, and career guidance during both phases of this proposal. Overall, these training experiences will be critical for me to successfully obtain an academic faculty position and establish my independent research program.
摘要 皮质中间神经元代表了一个广泛的类别的抑制性神经元是必不可少的控制大脑 兴奋性和协调行为。抑制回路的中断与许多大脑 这些疾病包括癫痫、智力残疾、自闭症、精神分裂症和头部损伤。最近,进步 在小鼠和人类干细胞研究中表明,多能细胞可用于产生富集的 皮质神经元和中间神经元的群体。然而,很少有研究系统地研究 来自干细胞来源的外源性抑制性神经元如何可能被用作细胞疗法来改变 体内神经回路这个K99/R 00应用程序的总体目标是确定皮层中间神经元如何 来源于小鼠和人的诱导多能干细胞(iPS细胞)功能性地并入到细胞中。 出生后的大脑该奖项的指导阶段将在加州大学旧金山弗朗西斯科进行 在Scott Baraban博士的指导下,该项目将在我自己的实验室继续进行, 独立教师的地位得到保障。在具体目标1和2中,我将使用基于发起人的报告人 纯化从iPS细胞产生的皮质中间神经元前体并表征其分化的构建体 在体外(目标1)和移植后(目标2),使用一系列的解剖,分子, 电生理学方法。在目标3(R 00阶段),我将确定iPS细胞的连接模式- 移植到出生后大脑的衍生中间神经元。了解皮层中间神经元是如何从 在功能上并入受体电路的干细胞来源将提供关于其 这是将这些发现转化为新的基于中间神经元的细胞的关键一步 治疗我的长期目标是建立一个独立的致力于了解神经机制, 电路组织和开发新的干细胞策略,用于脑修复和再生,特别是 与中间神经元功能障碍相关的脑疾病。这项研究将需要广泛的培训, 细胞生物学,和UCSF是一个优秀的机构,以完成本申请的指导阶段, 主要是由于丰富的杰出神经科学家和临床医生社区进行神经干细胞 研究和UCSF在干细胞领域的先驱作用。除了巴拉班博士出色的 作为导师,我组建了一个国际知名的科学家团队,他们将为我提供帮助- 技术培训、正式课程和职业指导。总的来说, 这些培训经验对我成功获得学术教职至关重要, 建立我的独立研究项目

项目成果

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Robert F Hunt其他文献

Robert F Hunt的其他文献

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{{ truncateString('Robert F Hunt', 18)}}的其他基金

Bidirectional control of Chd2 haploinsufficiency
Chd2 单倍体不足的双向控制
  • 批准号:
    10586860
  • 财政年份:
    2023
  • 资助金额:
    $ 8.8万
  • 项目类别:
Rewiring the Injured Brain with GABA Progenitors
用 GABA 祖细胞重新连接受损的大脑
  • 批准号:
    10211616
  • 财政年份:
    2016
  • 资助金额:
    $ 8.8万
  • 项目类别:
Rewiring the injured brain with GABA progenitors.
用 GABA 祖细胞重新连接受伤的大脑。
  • 批准号:
    9215702
  • 财政年份:
    2016
  • 资助金额:
    $ 8.8万
  • 项目类别:
Rewiring the Injured Brain with GABA Progenitors
用 GABA 祖细胞重新连接受损的大脑
  • 批准号:
    10367991
  • 财政年份:
    2016
  • 资助金额:
    $ 8.8万
  • 项目类别:
Rewiring the Injured Brain with GABA Progenitors
用 GABA 祖细胞重新连接受损的大脑
  • 批准号:
    10619546
  • 财政年份:
    2016
  • 资助金额:
    $ 8.8万
  • 项目类别:
Functional engraftment of stem cell-derived cortical interneurons
干细胞来源的皮质中间神经元的功能植入
  • 批准号:
    9266837
  • 财政年份:
    2015
  • 资助金额:
    $ 8.8万
  • 项目类别:
Functional engraftment of stem cell-derived cortical interneurons
干细胞来源的皮质中间神经元的功能植入
  • 批准号:
    8738733
  • 财政年份:
    2013
  • 资助金额:
    $ 8.8万
  • 项目类别:
Functional integration of inhibitory interneuron progenitors in the adult brain
成人大脑中抑制性中间神经元祖细胞的功能整合
  • 批准号:
    8452226
  • 财政年份:
    2012
  • 资助金额:
    $ 8.8万
  • 项目类别:
Functional integration of inhibitory interneuron progenitors in the adult brain
成人大脑中抑制性中间神经元祖细胞的功能整合
  • 批准号:
    8311375
  • 财政年份:
    2012
  • 资助金额:
    $ 8.8万
  • 项目类别:

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