Dual role for Headcase in hemocyte progenitor fate determination in Drosophila melanogaster.

IF 4 2区 生物学 Q1 GENETICS & HEREDITY
PLoS Genetics Pub Date : 2024-10-28 eCollection Date: 2024-10-01 DOI:10.1371/journal.pgen.1011448
Bayan Kharrat, Erika Gábor, Nikolett Virág, Rita Sinka, Ferenc Jankovics, Ildikó Kristó, Péter Vilmos, Gábor Csordás, Viktor Honti
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Abstract

The hematopoietic organ of the Drosophila larva, the lymph gland, is a simplified representation of mammalian hematopoietic compartments, with the presence of hemocyte progenitors in the medullary zone (MZ), differentiated hemocytes in the cortical zone (CZ), and a hematopoietic niche called the posterior signaling centre (PSC) that orchestrates progenitor differentiation. Our previous work has demonstrated that the imaginal cell factor Headcase (Hdc, Heca) is required in the hematopoietic niche to control the differentiation of hemocyte progenitors. However, the downstream mechanisms of Hdc-mediated hematopoietic control remained unknown. Here we show that Hdc exerts this function by negatively regulating the insulin/mTOR signaling in the niche. When Hdc is depleted in the PSC, the overactivation of this pathway triggers reactive oxygen species (ROS) accumulation and, in turn, the differentiation of effector lamellocytes non-cell-autonomously. Although overactivation of insulin/mTOR signaling normally leads to an increase in the size of the hematopoietic niche, this effect is concealed by cell death caused by hdc loss-of-function. Moreover, we describe here that hdc silencing in progenitors causes cell-autonomous ROS elevation and JNK pathway activation, resulting in decreased MZ size and differentiation of lamellocytes. Similarly to the PSC niche, knocking down hdc in the MZ also leads to caspase activation. Notably, depleting Hdc in the progenitors triggers proliferation, an opposing effect to what is observed in the niche. These findings further our understanding of how progenitor maintenance in the larval lymph gland is controlled autonomously and non-cell-autonomously, and point towards new mechanisms potentially regulating HSC maintenance across vertebrates.

黑腹果蝇血细胞祖细胞命运决定过程中 Headcase 的双重作用
果蝇幼虫的造血器官--淋巴腺--是哺乳动物造血分区的简化代表,髓质区(MZ)存在血细胞祖细胞,皮质区(CZ)存在分化的血细胞,还有一个称为后信号中心(PSC)的造血龛,负责协调祖细胞的分化。我们之前的研究表明,造血龛中需要显像细胞因子 Headcase(Hdc,Heca)来控制血细胞祖细胞的分化。然而,Hdc 介导造血控制的下游机制仍然未知。我们在这里发现,Hdc 是通过负向调节造血龛中的胰岛素/mTOR 信号来发挥这一功能的。当 Hdc 在 PSC 中耗竭时,该通路的过度激活会引发活性氧(ROS)积累,进而导致效应片层细胞的非细胞自主分化。虽然胰岛素/mTOR 信号的过度激活通常会导致造血龛的增大,但这种效应被 hdc 功能缺失导致的细胞死亡所掩盖。此外,我们在此描述了在祖细胞中沉默 hdc 会导致细胞自主性 ROS 升高和 JNK 通路激活,从而导致 MZ 大小减小和薄壁细胞分化。与 PSC 龛位类似,在 MZ 中敲除 hdc 也会导致 caspase 激活。值得注意的是,消耗祖细胞中的Hdc会引发增殖,这与在龛中观察到的效果相反。这些发现进一步加深了我们对幼虫淋巴腺中祖细胞维持是如何被自主和非细胞自主控制的理解,并指出了可能调控脊椎动物造血干细胞维持的新机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
PLoS Genetics
PLoS Genetics GENETICS & HEREDITY-
自引率
2.20%
发文量
438
期刊介绍: PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill). Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.
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