Laboratory of Immunology, Institute of Genetics, Biological Research Centre of the Hungarian Academy of Sciences, 6726 Szeged, Hungary.
Laboratory of Drosophila Germ Cell Differentiation, Institute of Genetics, Biological Research Centre of the Hungarian Academy of Sciences, 6726 Szeged, Hungary.
Genes (Basel). 2019 Mar 5;10(3):173. doi: 10.3390/genes10030173.
Due to the evolutionary conservation of the regulation of hematopoiesis, provides an excellent model organism to study blood cell differentiation and hematopoietic stem cell (HSC) maintenance. The larvae of respond to immune induction with the production of special effector blood cells, the lamellocytes, which encapsulate and subsequently kill the invader. Lamellocytes differentiate as a result of a concerted action of all three hematopoietic compartments of the larva: the lymph gland, the circulating hemocytes, and the sessile tissue. Within the lymph gland, the communication of the functional zones, the maintenance of HSC fate, and the differentiation of effector blood cells are regulated by a complex network of signaling pathways. Applying gene conversion, mutational analysis, and a candidate based genetic interaction screen, we investigated the role of Headcase (Hdc), the homolog of the tumor suppressor HECA in the hematopoiesis of . We found that naive loss-of-function mutant larvae produce lamellocytes, showing that Hdc has a repressive role in effector blood cell differentiation. We demonstrate that genetically interacts with the Hedgehog and the Decapentaplegic pathways in the hematopoietic niche of the lymph gland. By adding further details to the model of blood cell fate regulation in the lymph gland of the larva, our findings contribute to the better understanding of HSC maintenance.
由于造血的调控在进化上是保守的， 为研究血细胞分化和造血干细胞（HSC）维持提供了一个极好的模式生物。 的幼虫对免疫诱导做出反应，产生特殊的效应血细胞，即脂细胞，脂细胞包裹并随后杀死入侵物。脂细胞的分化是幼虫的三个造血区室（淋巴腺、循环血细胞和固着组织）协同作用的结果。在淋巴腺中，功能区的通讯、HSC 命运的维持和效应血细胞的分化受一个复杂的信号通路网络调控。通过基因转换、突变分析和基于候选基因的遗传互作筛选，我们研究了 Headcase（Hdc）在 的造血中的作用，Hdc 是肿瘤抑制因子 HECA 的同源物。我们发现，幼稚的失活 突变体幼虫会产生脂细胞，这表明 Hdc 在效应血细胞分化中起抑制作用。我们证明 在淋巴腺造血龛中与 Hedgehog 和 Decapentaplegic 途径存在遗传互作。通过进一步细化幼虫淋巴腺中血细胞命运调控的模型，我们的研究结果有助于更好地理解 HSC 的维持。
