Regional control of Drosophila gut stem cell proliferation: EGF establishes GSSC proliferative set point & controls emergence from quiescence.
Regional control of Drosophila gut stem cell proliferation: EGF establishes GSSC proliferative set point & controls emergence from quiescence.
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DOI：
10.1371/journal.pone.0080608
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Micchelli CA
中科院分区：
文献类型：
--
作者：
Strand M;Micchelli CA
成体干细胞的增殖速度差异很大。一些干细胞是组成性活跃的，而另一些干细胞只在损伤时分裂。控制这种差异增殖设定点的机制还不清楚。果蝇中肠的前-后（A/P）轴具有节段性组织，表现出生理上的区室化和区域特异性上皮。这些不同的中肠区域由具有独特分裂时间表的干细胞群维持，为研究这个问题提供了一个很好的实验模型。在这里，我们专注于静止的胃干细胞（GSSC）的酸性铜细胞区（CCR），表现出最大的潜伏期之间的所有特征的肠干细胞的分裂，以确定差异干细胞活性的分子基础。我们的分子遗传学分析表明，促有丝分裂EGF信号通路是一个限制因素控制GSSC增殖。我们发现，在基线条件下，当GSSC在很大程度上是静止的，最低水平的EGF配体在中肠被发现在CCR。然而，肠道病原体引起的急性上皮损伤导致CCR中EGF配体表达增加和GSSC谱系的快速扩增。因此，肠道干细胞在生理上不同的隔室中的独特增殖设定点由沿沿着A/P轴的小生境信号的区域控制来控制。
Adult stem cells vary widely in their rates of proliferation. Some stem cells are constitutively active, while others divide only in response to injury. The mechanism controlling this differential proliferative set point is not well understood. The anterior-posterior (A/P) axis of the adult Drosophila midgut has a segmental organization, displaying physiological compartmentalization and region-specific epithelia. These distinct midgut regions are maintained by defined stem cell populations with unique division schedules, providing an excellent experimental model with which to investigate this question. Here, we focus on the quiescent gastric stem cells (GSSCs) of the acidic copper cell region (CCR), which exhibit the greatest period of latency between divisions of all characterized gut stem cells, to define the molecular basis of differential stem cell activity. Our molecular genetic analysis demonstrates that the mitogenic EGF signaling pathway is a limiting factor controlling GSSC proliferation. We find that under baseline conditions, when GSSCs are largely quiescent, the lowest levels of EGF ligands in the midgut are found in the CCR. However, acute epithelial injury by enteric pathogens leads to an increase in EGF ligand expression in the CCR and rapid expansion of the GSSC lineage. Thus, the unique proliferative set points for gut stem cells residing in physiologically distinct compartments are governed by regional control of niche signals along the A/P axis.
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影响因子：
29.4
作者：
Mills JC;Shivdasani RA
通讯作者：
Shivdasani RA
DOI：
10.1126/science.1180794
发表时间：
2010-01-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li L;Clevers H
通讯作者：
Clevers H
DOI：
10.1073/pnas.1109794108
发表时间：
2011-10-25
影响因子：
11.1
作者：
Strand, Marie;Micchelli, Craig A.
通讯作者：
Micchelli, Craig A.
影响因子：
23.9
作者：
Jiang H;Grenley MO;Bravo MJ;Blumhagen RZ;Edgar BA
通讯作者：
Edgar BA
影响因子：
2.7
作者：
Beebe, Katherine;Lee, Wen-Chih;Micchelli, Craig A.
通讯作者：
Micchelli, Craig A.