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一组新的基因敲入小鼠确定了肠道干细胞中的 Notch 谱系和活性。

Notch lineages and activity in intestinal stem cells determined by a new set of knock-in mice.

机构信息

Morphogenesis and Intracellular Signaling, Institut Curie-UMR144 CNRS, Paris, France.

出版信息

PLoS One. 2011;6(10):e25785. doi: 10.1371/journal.pone.0025785. Epub 2011 Oct 3.

DOI:10.1371/journal.pone.0025785
PMID:21991352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3185035/
Abstract

The conserved role of Notch signaling in controlling intestinal cell fate specification and homeostasis has been extensively studied. Nevertheless, the precise identity of the cells in which Notch signaling is active and the role of different Notch receptor paralogues in the intestine remain ambiguous, due to the lack of reliable tools to investigate Notch expression and function in vivo. We generated a new series of transgenic mice that allowed us, by lineage analysis, to formally prove that Notch1 and Notch2 are specifically expressed in crypt stem cells. In addition, a novel Notch reporter mouse, Hes1-EmGFP(SAT), demonstrated exclusive Notch activity in crypt stem cells and absorptive progenitors. This roster of knock-in and reporter mice represents a valuable resource to functionally explore the Notch pathway in vivo in virtually all tissues.

摘要

Notch 信号在控制肠道细胞命运特化和稳态方面的保守作用已经得到了广泛的研究。然而,由于缺乏可靠的工具来研究 Notch 表达和功能在体内, Notch 信号在活跃的细胞中的确切身份以及不同 Notch 受体同源物在肠道中的作用仍然不清楚。我们生成了一系列新的转基因小鼠,通过谱系分析,正式证明 Notch1 和 Notch2 特异性表达于隐窝干细胞中。此外,一种新的 Notch 报告小鼠,Hes1-EmGFP(SAT),证明了 Notch 活性仅存在于隐窝干细胞和吸收祖细胞中。这些基因敲入和报告小鼠代表了一种有价值的资源,可以在体内实际上所有组织中对 Notch 途径进行功能探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b476/3185035/c688c372ed46/pone.0025785.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b476/3185035/f69ee9e94fc1/pone.0025785.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b476/3185035/b4ef27b4f756/pone.0025785.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b476/3185035/a00dedaa001e/pone.0025785.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b476/3185035/0f3967e68248/pone.0025785.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b476/3185035/c688c372ed46/pone.0025785.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b476/3185035/f69ee9e94fc1/pone.0025785.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b476/3185035/b4ef27b4f756/pone.0025785.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b476/3185035/a00dedaa001e/pone.0025785.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b476/3185035/0f3967e68248/pone.0025785.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b476/3185035/c688c372ed46/pone.0025785.g005.jpg

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PLoS Comput Biol. 2011 Jan 6;7(1):e1001045. doi: 10.1371/journal.pcbi.1001045.
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