bantam miRNA is important for Drosophila blood cell homeostasis and a regulator of proliferation in the hematopoietic progenitor niche.
bantam miRNA is important for Drosophila blood cell homeostasis and a regulator of proliferation in the hematopoietic progenitor niche.
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DOI：
10.1016/j.bbrc.2014.09.109
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发表时间：
2014-10-24
影响因子：
3.1
通讯作者：
Schulz RA
中科院分区：
文献类型：
--
作者：
Lam V;Tokusumi T;Tokusumi Y;Schulz RA
本研究利用果蝇的造血系统，对造血祖细胞生态位在血液发育中的生长控制过程进行了新的研究。生态位微环境是控制祖细胞群体和分化的成熟血细胞之间平衡的重要组成部分，并且已显示当失调时会导致人类造血系统恶性肿瘤。microRNA是一类与血液恶性肿瘤相关的调节因子;然而，关于miRNA在利基中的作用的信息仍然相对缺乏。在这里，我们证明，矮脚鸡的miRNA是内源性活跃的果蝇造血祖细胞龛，后部信号中心（PSC），并在主要的造血器官，淋巴腺，作为一个积极的调节生长的功能。矮脚鸡的损失导致PSC和总体淋巴腺大小的显著减小，以及祖细胞群体的损失和成熟血细胞的相关过早分化。有趣的是，除了对适当的淋巴腺发育至关重要之外，我们已经确定bantam是PSC中胰岛素信号级联的新型上游组分，并且已经揭示了dMyc是bantam活性的一个核心因子。这些重要的发现确定矮脚鸡作为一种新的造血调节剂，将其置于进化上保守的信号通路中，提出了一种调节方式，并提供了一种机制，通过该机制促进造血生态位中的细胞增殖。
The Drosophila hematopoietic system is utilized in this study to gain novel insights into the process of growth control of the hematopoietic progenitor niche in blood development. The niche microenvironment is an essential component controlling the balance between progenitor populations and differentiated, mature blood cells and has been shown to lead to hematopoietic malignancies in humans when misregulated. MicroRNAs are one class of regulators associated with blood malignancies; however, there remains a relative paucity of information about the role of miRNAs in the niche. Here we demonstrate that bantam miRNA is endogenously active in the Drosophila hematopoietic progenitor niche, the posterior signaling center (PSC), and functions in the primary hematopoietic organ, the lymph gland, as a positive regulator of growth. Loss of bantam leads to a significant reduction in the PSC and overall lymph gland size, as well as a loss of the progenitor population and correlative premature differentiation of mature hemocytes. Interestingly, in addition to being essential for proper lymph gland development, we have determined bantam to be a novel upstream component of the insulin signaling cascade in the PSC and have unveiled dMyc as one factor central to bantam activity. These important findings identify bantam as a new hematopoietic regulator, place it in an evolutionarily conserved signaling pathway, present one way in which it is regulated, and provide a mechanism through which it facilitates cellular proliferation in the hematopoietic niche.
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DOI：
10.1084/jem.20090831
发表时间：
2010-03-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Han YC;Park CY;Bhagat G;Zhang J;Wang Y;Fan JB;Liu M;Zou Y;Weissman IL;Gu H
通讯作者：
Gu H
影响因子：
9.8
作者：
Crozatier M;Ubeda JM;Vincent A;Meister M
通讯作者：
Meister M
影响因子：
9.2
作者：
Boulan, Laura;Martin, David;Milan, Marco
通讯作者：
Milan, Marco
影响因子：
64.5
作者：
Böhni, R;Riesgo-Escovar, J;Hafen, E
通讯作者：
Hafen, E
影响因子：
--
作者：
Kramer, Jamie M;Davidge, Jason T;Staveley, Brian E
通讯作者：
Staveley, Brian E