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中文摘要
翻译
在成人中,组织的维持和修复依赖于稳定的干细胞群
英文摘要
In adults, tissue maintenance and repair depends on a stable population of stem cells that can give rise to both self-renewing and differentiating daughter cells. An understanding of how this process is regulated is of fundamental importance because an excess of differentiation can lead to stem cell depletion and tissue senescence, while a failure to enter the differentiation pathway can lead to an accumulation of proliferating cells and tumor formation. A comparison of male and female germline stem cell (GSC) behavior in Drosophila ovaries and testis, two of the premier model systems for the study of stem cells in their natural environment, reveals sexually dimorphic adaptations of the regulatory mechanisms governing the self-renewal/differentiation decision. Little attention, however, has been paid to how these differences are achieved. Data emerging from the Salz lab supports a novel model in which the female specific RNA binding protein Sex-lethal (Sxl) jointly controls sexual identity and the self- renewal/differentiation decision in the germline. GSCs without Sxl protein fail to successfully execute the self-renewal to differentiation cell fate switch. The failure to differentiate is accompanied by the inappropriate expression of a set of male specific markers, continued proliferation and formation of a tumor. Sxl encodes a ubiquitously expressed female-specific RNA binding protein. In somatic cells it globally regulates all aspects of female-specific development and behavior. Its mode of action in the germline, however, remains poorly understood. The studies in this new proposal address this issue using an integrated experimental approach that combines classical and molecular genetics with RNA/protein biochemistry. Specifically, we focus on how Sxl maintains sexual identity, beginning with preliminary studies showing that Sxl acts through the Jak/Stat signaling pathway to repress male-specific germ cell behavior. The knowledge generated by the studies in this proposal will illuminate the intrinsic regulatory mechanisms that integrates sexual identity and the self-renewal/differentiation decision, and will provide information about why disruptions in this pathway lead to germ cell tumors. Information from model systems such as the Drosophila germline will provide key insights into how stem cells control the self-renewal/differentiation decision in other, less experimentally tractable systems. More generally, the information gained from our animal model studies will illuminate strategies used by RNA regulators to differentially regulate gene expression in time and space.
期刊论文(4)
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会议论文
Testicular teratomas: Germ cells cycling in the wrong direction.
睾丸畸胎瘤:生殖细胞以错误的方向循环。
DOI: 10.1080/15384101.2016.1154369
发表时间: 2016
期刊: Cell cycle (Georgetown, Tex.)
影响因子: --
作者: [Salz,HelenK]
通讯作者: Salz,HelenK
DOI: 10.1038/s41467-018-06697-x
发表时间: 2018-10-08
期刊: Nature communications
影响因子: 16.6
作者: [Smolko AE, Shapiro-Kulnane L, Salz HK]
通讯作者: Salz HK
DOI: 10.1002/mrd.22779
发表时间: 2017-03
期刊: Molecular reproduction and development
影响因子: 2.5
作者: [Salz HK, Dawson EP, Heaney JD]
通讯作者: Heaney JD
H3K9me3-based gene silencing and cellular identity
  • 批准号:
    10548567
  • 项目类别:
  • 资助金额:
    $42.25万
  • 财政年份:
    2023
  • 负责人:
    HELEN Karen SALZ
  • 依托单位:
Sexual Identity Maintenance in Drosophila Female Germ Cells
  • 批准号:
    10241355
  • 项目类别:
  • 资助金额:
    $32.2万
  • 财政年份:
    2018
  • 负责人:
    HELEN Karen SALZ
  • 依托单位:
Sexual identity and germ cell differentiation in the Drosophila ovary
  • 批准号:
    8892205
  • 项目类别:
  • 资助金额:
    $30.12万
  • 财政年份:
    2013
  • 负责人:
    HELEN Karen SALZ
  • 依托单位:
Sexual identity and germ cell differentiation in the Drosophila ovary
  • 批准号:
    8503678
  • 项目类别:
  • 资助金额:
    $30.12万
  • 财政年份:
    2013
  • 负责人:
    HELEN Karen SALZ
  • 依托单位:
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