JAK/STAT signaling coordinates stem cell proliferation and multilineage differentiation in the Drosophila intestinal stem cell lineage
JAK/STAT signaling coordinates stem cell proliferation and multilineage differentiation in the Drosophila intestinal stem cell lineage
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DOI：
10.1016/j.ydbio.2009.10.045
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发表时间：
2010-02-01
影响因子：
2.7
通讯作者：
Micchelli, Craig A.
中科院分区：
文献类型：
--
作者：
Beebe, Katherine;Lee, Wen-Chih;Micchelli, Craig A.
成年斯坦细胞是一个谱系中最原始的细胞，其特点是自我更新和多能性。干细胞增殖和多系分化的协调控制是确保稳定输出分化子细胞以维持组织稳态所必需的。然而，我们对协调干细胞增殖和子细胞分化的信号知之甚少。在这里，我们研究了保守的JAK/STAT信号通路在果蝇肠干细胞（ISC）谱系中的作用。我们首先发现，JAK/STAT信号通常在ISCs及其新形成的子细胞中活跃，但在终末分化的肠内分泌（ee）细胞或肠细胞（EC）细胞中不活跃。其次，对ISC谱系的分析表明，JAK/STAT信号对于子细胞分化是必要的，但不是充分的，这表明进行多谱系分化的能力取决于JAK/STAT。最后，我们的分析表明JAK/STAT信号是ISC增殖的有效调节剂，但不是ISC自我更新的调节剂。基于这些发现，我们提出了一个JAK/STAT信号协调干细胞增殖过程和子细胞进行多谱系分化的能力的模型，确保了谱系中强大的细胞输出。(C) 2009爱思唯尔公司版权所有。
Adult stein cells are the most primitive cells of a lineage and are distinguished by the properties of self-renewal and multipotency. Coordinated control of stem cell proliferation and multilineage differentiation is essential to ensure a steady output of differentiated daughter cells necessary to maintain tissue homeostasis. However, little is known about the signals that coordinate stem cell proliferation and daughter cell differentiation. Here we investigate the role of the conserved JAK/STAT signaling pathway in the Drosophila intestinal stem cell (ISC) lineage. We show first, that JAK/STAT signaling is normally active in both ISCs and their newly formed daughters, but not in terminally differentiated enteroendocrine (ee) cells or enterocyte (EC) cells. Second, analysis of ISC lineages shows that JAK/STAT signaling is necessary but not sufficient for daughter cell differentiation, indicating that competence to undergo multilineage differentiation depends upon JAK/STAT. Finally, our analysis reveals JAK/STAT signaling to be a potent regulator of ISC proliferation, but not ISC self-renewal. On the basis of these findings, we suggest a model in which JAK/STAT signaling coordinates the processes of stem cell proliferation with the competence of daughter cells to undergo multilineage differentiation, ensuring a robust cellular output in the lineage. (C) 2009 Elsevier Inc. All rights reserved.