Drosophila Myc integrates multiple signaling pathways to regulate intestinal stem cell proliferation during midgut regeneration
Drosophila Myc integrates multiple signaling pathways to regulate intestinal stem cell proliferation during midgut regeneration
复制标题
果蝇Myc整合多种信号通路来调节中肠再生过程中肠道干细胞的增殖
DOI：
10.1038/cr.2013.101
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发表时间：
2013-07
期刊：
影响因子：
44.1
通讯作者：
Jiang, Jin
中科院分区：
文献类型：
--
作者：
Jiang, Alice;Ip, Y. Tony;Jiang, Huaqi;Jiang, Jin
果蝇成体中肠的肠干细胞（ISCs）对维持组织内环境稳定至关重要，它们的增殖和分化加速以满足对损伤后丢失细胞的补充需求。包括JAK-STAT、EGFR和Hippo（Hpo）通路在内的几种信号通路已被证明与损伤诱导的ISC增殖有关，但整合这些通路的机制仍不清楚。在这里，我们证明了果蝇同源的癌蛋白Myc（dMyc）的功能下游的这些信号通路，以介导其对ISC增殖的影响。dMyc在前体细胞中的表达响应于组织损伤而被刺激，并且dMyc对于加速ISC增殖和中肠再生是必不可少的。我们发现，葡聚糖硫酸钠喂养引起的组织损伤通过Hpo途径刺激dMyc表达，而博来霉素喂养通过JAK-STAT和EGFR途径激活dMyc。我们提供的证据表明，dMyc的表达是转录上调的多种信号转导途径，这是必要的最佳ISC增殖，以应对组织损伤。我们还获得了组织损伤可以在转录后上调dMyc表达的证据。最后，我们表明，基础水平的dMyc表达是必需的ISC的维护，增殖和谱系分化在正常组织的稳态。
Intestinal stem cells (ISCs) in the Drosophila adult midgut are essential for maintaining tissue homeostasis, and their proliferation and differentiation speed up in order to meet the demand for replenishing the lost cells in response to injury. Several signaling pathways including JAK-STAT, EGFR and Hippo (Hpo) pathways have been implicated in damage-induced ISC proliferation, but the mechanisms that integrate these pathways have remained elusive. Here, we demonstrate that the Drosophila homolog of the oncoprotein Myc (dMyc) functions downstream of these signaling pathways to mediate their effects on ISC proliferation. dMyc expression in precursor cells is stimulated in response to tissue damage, and dMyc is essential for accelerated ISC proliferation and midgut regeneration. We show that tissue damage caused by dextran sulfate sodium feeding stimulates dMyc expression via the Hpo pathway, whereas bleomycin feeding activates dMyc through the JAK-STAT and EGFR pathways. We provide evidence that dMyc expression is transcriptionally upregulated by multiple signaling pathways, which is required for optimal ISC proliferation in response to tissue damage. We have also obtained evidence that tissue damage can upregulate dMyc expression post-transcriptionally. Finally, we show that a basal level of dMyc expression is required for ISC maintenance, proliferation and lineage differentiation during normal tissue homeostasis.
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DOI：
10.1083/jcb.201103018
发表时间：
2011-05-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Amcheslavsky A;Ito N;Jiang J;Ip YT
通讯作者：
Ip YT
影响因子：
2.7
作者：
Pierce, Sarah B.;Yost, Cynthia;Eisenman, Robert N.
通讯作者：
Eisenman, Robert N.
影响因子：
64.5
作者：
Moreno, E;Basler, K
通讯作者：
Basler, K
影响因子：
11.8
作者：
Neto-Silva, Ricardo M.;de Beco, Simon;Johnston, Laura A.
通讯作者：
Johnston, Laura A.
影响因子：
64.8
作者：
Sansom, Owen J.;Meniel, Valerie S.;Clarke, Alan R.
通讯作者：
Clarke, Alan R.