Gene regulatory networks controlling hematopoietic progenitor niche cell production and differentiation in the Drosophila lymph gland.
Gene regulatory networks controlling hematopoietic progenitor niche cell production and differentiation in the Drosophila lymph gland.
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DOI：
10.1371/journal.pone.0041604
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Schulz RA
中科院分区：
文献类型：
--
作者：
Tokusumi Y;Tokusumi T;Shoue DA;Schulz RA
在果蝇中，造血发生在两个阶段，第一个阶段在胚胎发育期间完成，第二个阶段在幼虫发育期间完成。淋巴腺作为最终造血程序的场所，这种幼虫组织的细胞组织和遗传调节已得到充分研究。虽然髓带含有干细胞样造血祖细胞，但后部信号中心（PSC）作为控制祖细胞维持与细胞分化之间的决定所必需的生态位微环境起作用。在这份报告中，我们利用PSC特异性GAL4驱动和UAS基因RNAi菌株，选择性地敲低PSC细胞中的单个基因功能。我们评估了废除820个基因的功能对小生境细胞产生和分化的影响。100个基因被证明是必要的正常生态位的发展，与不同的基因座放置到亚组的基础上，其编码的蛋白质产品的功能和已知的遗传相互作用。对于其中三组的成员，我们表征了功能丧失和获得的表型。BAP染色质重塑复合物成员的基因功能敲低导致不表达刺猬（hh）基因的小生境细胞，并且不能分化丝状伪足，这被认为对Hh信号从小生境到祖细胞是重要的。废除胰岛素样生长因子和TOR信号通路的各种成员的基因功能导致PSC细胞产生异常，导致有缺陷的生态位组织。对Pten、TSC1和TSC2肿瘤抑制基因的进一步分析表明，它们的功能丧失状况导致血细胞稳态的严重改变，包括板层细胞的大量产生，板层细胞是参与先天性免疫应答的特化血细胞。总之，这种细胞特异性RNAi敲除调查和突变体表型分析鉴定了淋巴腺内造血祖细胞生态位的正常组织和功能所需的多个基因及其调控网络。
Hematopoiesis occurs in two phases in Drosophila, with the first completed during embryogenesis and the second accomplished during larval development. The lymph gland serves as the venue for the final hematopoietic program, with this larval tissue well-studied as to its cellular organization and genetic regulation. While the medullary zone contains stem-like hematopoietic progenitors, the posterior signaling center (PSC) functions as a niche microenvironment essential for controlling the decision between progenitor maintenance versus cellular differentiation. In this report, we utilize a PSC-specific GAL4 driver and UAS-gene RNAi strains, to selectively knockdown individual gene functions in PSC cells. We assessed the effect of abrogating the function of 820 genes as to their requirement for niche cell production and differentiation. 100 genes were shown to be essential for normal niche development, with various loci placed into sub-groups based on the functions of their encoded protein products and known genetic interactions. For members of three of these groups, we characterized loss- and gain-of-function phenotypes. Gene function knockdown of members of the BAP chromatin-remodeling complex resulted in niche cells that do not express the hedgehog (hh) gene and fail to differentiate filopodia believed important for Hh signaling from the niche to progenitors. Abrogating gene function of various members of the insulin-like growth factor and TOR signaling pathways resulted in anomalous PSC cell production, leading to a defective niche organization. Further analysis of the Pten, TSC1, and TSC2 tumor suppressor genes demonstrated their loss-of-function condition resulted in severely altered blood cell homeostasis, including the abundant production of lamellocytes, specialized hemocytes involved in innate immune responses. Together, this cell-specific RNAi knockdown survey and mutant phenotype analyses identified multiple genes and their regulatory networks required for the normal organization and function of the hematopoietic progenitor niche within the lymph gland.
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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：
21.3
作者：
通讯作者：
--
DOI：
10.1084/jem.20081297
发表时间：
2008-09-29
期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
2.7
作者：
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通讯作者：
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影响因子：
11.8
作者：
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