Role of interdigitating secretory cells in regulation of intestinal stem cells during development

指状分泌细胞在发育过程中肠干细胞调节中的作用

基本信息

  • 批准号:
    9351670
  • 负责人:
  • 金额:
    $ 42.39万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-08-05 至 2022-06-30
  • 项目状态:
    已结题

项目摘要

Summary/Abstract While the structure of the adult intestinal stem cell niche has become well defined, little is know about the structure and regulation of the immature stem cell niche. In the adult mammalian crypt, dedicated stem cells are referred to as Crypt Base Columnar (CBC) cells are regulated by interdigitated Paneth cells in the small intestine and a subtype of goblet cells in the large intestine. Here we propose that the immature stem cell compartment is regulated by cells analogous to the Paneth and goblet cells, that regulate growth and transformation of an immature stem cell niche into the adult structure. Using the advantages of external development and transparency of the zebrafish model system to manipulate and visualize the developing intestine, we identify regulatory cells within the immature stem cell compartment, which differentiate at the fold base beginning at the end of embryogenesis and continuing through juvenile phase. Preliminary data indicates that these cells are involved negative regulation of epithelial proliferation and there are two different groups, one group that differentiates during the first half of juvenile period and a second group that forms as the intestine matures to the adult structure. In Aim 1 we will focus on disrupting the function of these cells to determine their role in regulation of the architecture of the developing stem cell compartment leading up to maturation of the adult intestinal stem cell compartment. In Aim 2 we will determine whether the identified regulatory cells modulate epithelial proliferation by modulating the Wnt pathway. Finally, in Aim 3, we will determine whether thyroid hormone plays a role in differentiation of the group of regulatory cells that differentiates as the intestine matures to the adult structure. Together, these studies will identify new features of the network controlling growth of the immature stem cell compartment as it matures into the adult structure. In the long term, this work has the potential to shed light on intestinal diseases resulting from congenital defects due to errors during establishment of the intestinal epithelial stem cell compartment.
摘要/文摘

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Development and organization of the zebrafish intestinal epithelial stem cell niche.
A novel group of secretory cells regulates development of the immature intestinal stem cell niche through repression of the main signaling pathways driving proliferation.
一组新的分泌细胞通过抑制驱动增殖的主要信号通路来调节未成熟肠道干细胞生态位的发育。
  • DOI:
    10.1016/j.ydbio.2019.08.005
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    2.7
  • 作者:
    Li,Jianlong;Dedloff,MargaretR;Stevens,Katrina;Maney,Lea;Prochaska,Morgan;Hongay,CintiaF;Wallace,KennethN
  • 通讯作者:
    Wallace,KennethN
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KENNETH N WALLACE其他文献

KENNETH N WALLACE的其他文献

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{{ truncateString('KENNETH N WALLACE', 18)}}的其他基金

Regulation of developing intestinal stem cells by unique secretory cells
独特的分泌细胞对发育中的肠道干细胞的调节
  • 批准号:
    10438109
  • 财政年份:
    2022
  • 资助金额:
    $ 42.39万
  • 项目类别:
Development and Functional Analysis of Components of the Zebrafish Serotonin Sign
斑马鱼血清素标志成分的开发和功能分析
  • 批准号:
    7981554
  • 财政年份:
    2010
  • 资助金额:
    $ 42.39万
  • 项目类别:
Development and Functional Analysis of Components of the Zebrafish Serotonin Sign
斑马鱼血清素标志成分的开发和功能分析
  • 批准号:
    8547892
  • 财政年份:
    2010
  • 资助金额:
    $ 42.39万
  • 项目类别:
Development of Zebrafish Enteric Nervous System and Intestinal Smooth Muscle
斑马鱼肠神经系统和肠平滑肌的发育
  • 批准号:
    7195477
  • 财政年份:
    2007
  • 资助金额:
    $ 42.39万
  • 项目类别:

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