CONTROL OF STEM CELL FATE IN DROSOPHILA SPERMATOGENESIS
果蝇精子发生中干细胞命运的控制
基本信息
- 批准号:6536325
- 负责人:
- 金额:$ 17.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-04-01 至 2004-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION: (Scanned from the applicant's abstract) Spermatogenesis relies on
the establishment and maintenance of a stem cell population within the testis.
Although spermatogonial stem cells are essential for reproduction, little is
known about their regulation. Environmental cues from nearby cells are thought
to be crucial for stem cell maintenance, but identifying them is extremely
challenging in mammalian systems. Drosophila spermatogenesis provides an
excellent model system for studying stem cell regulation, since spermatogonial
stem cells can be identified, and genetics can be used to systematically
identify regulatory molecules. In this proposal the role of the highly
conserved Jak-STAT signal transduction pathway in stem cell maintenance is
examined. The Jak kinase homologue Hopscotch (Hop) is required for stem cell
maintenance, and overactivation of the Jak-Stat signaling pathway leads to
ectopic cells with stem cell character. Also, the ligand activating Jak-STAT is
present in a small group of somatic cells, called the hub, to which the stem
cells are anchored. This leads to the hypothesis that the hub comprises a stem
cell niche, or specialized local environment, that instructs nearby cells to
retain a stem cell fate by activating the Jak-STAT pathway within these cells.
To test this hypothesis, the precise role of Jak-STAT signaling in the niche
will be examined. In Aim 1, marked loss-of-function clones will be generated to
determine if stem cells directly require Jak-STAT signaling. In Aim 2, both
loss-of-function and ectopic expression of Jak-Stat signaling molecules will
test whether Jak-STAT signaling instructs stem cell fate or, alternatively, is
required to permit stem cell viability. In Aim 3, the role of Jak-STAT
signaling in limiting stem cell numbers in the niche will be studied. Finally,
since it is likely that other factors act either in concert with Jak-STAT, or
subsequent to it in maintaining the stem cell niche, we employ genetic
approaches to systematically identify these factors in Aim 4. Since Drosophila
and mammalian spermatogenesis are conserved, the regulatory mechanisms
uncovered in this proposal will likely add to the understanding of the
regulation of stem cells residing in more complex and less defined
environments, such as mammalian spermatogonial stem cells, which are essential
for human fertility.
描述:(从申请人的摘要中扫描)精子发生依赖于
睾丸中干细胞种群的建立和维护。
尽管精子干细胞对于繁殖至关重要,但几乎没有
知道他们的调节。认为附近细胞的环境提示
对于干细胞维护至关重要,但是识别它们非常
在哺乳动物系统中具有挑战性。果蝇的精子发生提供了
由于精子量,用于研究干细胞调节的出色模型系统
可以识别干细胞,遗传学可用于系统地
确定调节分子。在这个提议中,高度的角色
保守的JAK-STAT信号转导途径是干细胞维护中的
检查。干细胞需要JAK激酶同源物Hopscotch(HOP)
维护和过度激活JAK-STAT信号通路导致
异位细胞具有干细胞特征。另外,配体激活jak-stat是
存在于一小部分的体细胞中,称为轮毂,茎上
细胞是锚定的。这导致了一个假说,即轮毂包含一个茎
细胞生态位或专门的当地环境,指示附近的细胞
通过激活这些细胞内的JAK-Stat途径来保留干细胞命运。
为了检验这一假设,jak-stat信号在利基市场中的确切作用
将被检查。在AIM 1中,将生成明显的功能丧失克隆
确定干细胞是否直接需要JAK-STAT信号传导。在AIM 2中,两者都
Jak-Stat信号分子的功能丧失和异位表达将
测试JAK-STAT信号是否指示干细胞命运还是
允许干细胞生存能力所需。在AIM 3中,Jak-Stat的角色
将研究利基中限制干细胞数中的信号传导。最后,
由于其他因素可能与Jak-STAT一起起作用,或者
在维持干细胞生态位时,我们采用了遗传
在目标4中系统地识别这些因素的方法。因为果蝇
和哺乳动物的精子发生是保守的,是调节机制
在本提案中发现的可能会增加对
居住在更复杂且定义较低的干细胞的调节
环境,例如哺乳动物精子干细胞,这是必不可少的
用于人类生育。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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数据更新时间:2024-06-01
Erika L Matunis的其他基金
Regulation of cellular plasticity and regeneration in Drosophila spermatogenesis
果蝇精子发生中细胞可塑性和再生的调节
- 批准号:1016092610160926
- 财政年份:2020
- 资助金额:$ 17.3万$ 17.3万
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Regulation of cellular plasticity and regeneration in Drosophila spermatogenesis
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- 批准号:1063112510631125
- 财政年份:2020
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Regulation of cellular plasticity and regeneration in Drosophila spermatogenesis
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- 批准号:1043192810431928
- 财政年份:2020
- 资助金额:$ 17.3万$ 17.3万
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Control of Stem Cell Fate in Drosophila Spermatogenesis
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- 批准号:93545029354502
- 财政年份:2016
- 资助金额:$ 17.3万$ 17.3万
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- 批准号:91553289155328
- 财政年份:2016
- 资助金额:$ 17.3万$ 17.3万
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Cellular plasticity in the Drosophila spermatogonial stem cell niche
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- 批准号:79351477935147
- 财政年份:2009
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- 项目类别:
Cellular plasticity in the Drosophila spermatogonial stem cell niche
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- 批准号:84233008423300
- 财政年份:2007
- 资助金额:$ 17.3万$ 17.3万
- 项目类别:
Cellular plasticity in the Drosophila spermatogonial stem cell niche
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- 批准号:73645637364563
- 财政年份:2007
- 资助金额:$ 17.3万$ 17.3万
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Cellular plasticity in the Drosophila spermatogonial stem cell niche
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- 财政年份:2007
- 资助金额:$ 17.3万$ 17.3万
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Cellular plasticity in the Drosophila spermatogonial stem cell niche
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- 财政年份:2007
- 资助金额:$ 17.3万$ 17.3万
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