Origin and dynamic lineage characteristics of the developing Drosophila midgut stem cells.
Origin and dynamic lineage characteristics of the developing Drosophila midgut stem cells.
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DOI：
10.1016/j.ydbio.2016.06.018
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发表时间：
2016-08
影响因子：
2.7
通讯作者：
S. Takashima;Patrick Aghajanian;A. Younossi‐Hartenstein;V. Hartenstein
中科院分区：
文献类型：
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作者：
S. Takashima;Patrick Aghajanian;A. Younossi‐Hartenstein;V. Hartenstein
消化性肠干细胞（ISCs）产生果蝇中肠的所有细胞类型，包括肠细胞、内分泌细胞和腺细胞（例如，铜细胞），贯穿动物的一生。在控制ISC自我更新和不同细胞类型产生之间平衡的信号传导机制中，Notch（N）起着关键作用。在本文中，我们研究了ISCs的出现在变态和N在这个过程中的作用。果蝇成体肠干细胞（drosophilaadult intestinal stem cells，pISCs）的前体细胞在变态开始后的最初几个小时内首先在蛹的中肠中被检测到，为能动的间充质细胞。pISC执行2-3轮的准异步除法。第一次有丝分裂仅产生pISC数目的增加。在接下来的几轮有丝分裂中，分裂的pISCs产生更多的pISCs，以及填充羽化蝇中肠的内分泌细胞。肠上皮细胞直到羽化前后才出现在pISC子代中。从蛹中期开始在pISC中表达的“前内分泌”基因pros（pros）负责推进这些细胞中的内分泌命运;去除pros后，pISC继续增殖，但内分泌细胞不形成。相反，pISCs中pross的表达在pross开始时开始受到N活性的限制。N的丧失废除了增殖，并在所有pISC中开启了内分泌命运。我们的研究结果表明，开关依赖于活性的N和pasacts在pISC的水平，以决定之间的持续增殖和内分泌分化。
Proliferating intestinal stem cells (ISCs) generate all cell types of theDrosophilamidgut, including enterocytes, endocrine cells, and gland cells (e.g., copper cells), throughout the lifetime of the animal. Among the signaling mechanisms controlling the balance between ISC self-renewal and the production of different cell types, Notch (N) plays a pivotal role. In this paper we investigated the emergence of ISCs during metamorphosis and the role of N in this process. Precursors of theDrosophilaadult intestinal stem cells (pISCs) can be first detected within the pupal midgut during the first hours after onset of metamorphosis as motile mesenchymal cells. pISCs perform 2–3 rounds of parasynchronous divisions. The first mitosis yields only an increase in pISC number. During the following rounds of mitosis, dividing pISCs give rise to more pISCs, as well as the endocrine cells that populate the midgut of the eclosing fly. Enterocytes do not appear among the pISC progeny until around the time of eclosion. The “proendocrine” geneprospero (pros), expressed from mid-pupal stages onward in pISCs, is responsible to advance the endocrine fate in these cells; following removal ofpros, pISCs continue to proliferate, but endocrine cells do not form. Conversely, the onset of N activity that occurs around the stage whenproscomes on restrictsprosexpression among pISCs. Loss of N abrogates proliferation and switches on an endocrine fate among all pISCs. Our results suggest that a switch depending on the activity of N andprosacts at the level of the pISC to decide between continued proliferation and endocrine differentiation.