Dpp dependent Hematopoietic stem cells give rise to Hh dependent blood progenitors in larval lymph gland of Drosophila.
Dpp dependent Hematopoietic stem cells give rise to Hh dependent blood progenitors in larval lymph gland of Drosophila.
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DOI：
10.7554/elife.18295
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发表时间：
2016-10-26
期刊：
影响因子：
7.7
通讯作者：
Mandal L
中科院分区：
文献类型：
--
作者：
Dey NS;Ramesh P;Chugh M;Mandal S;Mandal L
果蝇的造血作用与脊椎动物的造血作用在不同的阶段和信号分子方面都非常相似。尽管如此，在果蝇中还没有造血干细胞（HSC）的证据，幼虫淋巴腺及其依赖刺猬的祖细胞充当了祖细胞生物学的无脊椎动物模型。通过谱系追踪分析，我们现已在一龄幼虫淋巴腺中鉴定出表达 Notch 的 HSC。我们的研究清楚地建立了表达Notch的HSC和之前描述的表达Domeless的祖细胞之间的层次关系。这些 HSC 需要来自造血生态位的十五带 (Dpp) 信号来维持，其维持方式与脊椎动物主动脉-性腺-中肾 (AGM) HSC 相同。因此，这项研究不仅扩大了这些不同类群的保护范围，而且还提供了一个新模型，可用于更好地了解 AGM 相关的造血干细胞 (HSC)。血细胞在动物中发挥着许多重要作用，包括在身体各处输送氧气和防御入侵的微生物。人类等脊椎动物和果蝇的血细胞发育有许多相似之处。因此，研究人员经常使用果蝇作为模型来研究脊椎动物如何制造新血细胞。果蝇幼虫在淋巴腺中从“祖”细胞中产生新的血细胞，这些细胞与脊椎动物中产生血细胞的干细胞（称为造血干细胞，简称 HSC）有一些相似之处。祖细胞生长并分裂，随后发育成成熟的血细胞。祖细胞的命运取决于作为其生态位的相邻一组特化细胞产生的信号。例如，从生态位中释放出一种名为 Hedgehog 的信号蛋白来维持祖细胞。另一方面，脊椎动物中的 HSC 依赖另一种称为 BMP 的信号蛋白来维持它们。尽管淋巴腺中的祖细胞被认为表现得像脊椎动物干细胞，但尚不清楚果蝇是否也有造血干细胞群。戴伊等人。研究了果蝇幼虫淋巴腺细胞的命运。实验揭示了淋巴腺中的一组新细胞，其行为类似于脊椎动物干细胞并产生祖细胞。由于新发现的细胞也依赖于利基来维持，Dey 等人。将它们命名为 HSC。进一步的实验表明，与脊椎动物中的 HSC 一样，果蝇 HSC 使用 Dpp（BMP 的果蝇等效物）作为生态位信号。下一个挑战是使用果蝇造血干细胞作为模型来研究脊椎动物的血液如何发育，以及血液疾病患者的血液如何改变。
Drosophila hematopoiesis bears striking resemblance with that of vertebrates, both in the context of distinct phases and the signaling molecules. Even though, there has been no evidence of Hematopoietic stem cells (HSCs) in Drosophila, the larval lymph gland with its Hedgehog dependent progenitors served as an invertebrate model of progenitor biology. Employing lineage-tracing analyses, we have now identified Notch expressing HSCs in the first instar larval lymph gland. Our studies clearly establish the hierarchical relationship between Notch expressing HSCs and the previously described Domeless expressing progenitors. These HSCs require Decapentapelagic (Dpp) signal from the hematopoietic niche for their maintenance in an identical manner to vertebrate aorta-gonadal-mesonephros (AGM) HSCs. Thus, this study not only extends the conservation across these divergent taxa, but also provides a new model that can be exploited to gain better insight into the AGM related Hematopoietic stem cells (HSCs). Blood cells perform many important roles in animals, including transporting oxygen around the body and defending against invading microbes. There are many similarities between how blood cells develop in vertebrate animals, such as humans, and in fruit flies. Therefore, researchers often use fruit flies as models to study how vertebrates make new blood cells. Fruit fly larvae produce new blood cells in the lymph gland from “progenitor” cells that show several similarities to the stem cells that make blood cells in vertebrates, known as Hematopoietic Stem Cells (or HSCs for short). The progenitor cells grow and divide and subsequently develop into mature blood cells. The fate of the progenitor cells depend on signals produced from an adjoining group of specialized cells that serve as its niche. For example, a signal protein called Hedgehog delivered from the niche maintains the progenitor cells. On the other hand, HSCs in vertebrates rely on another signal protein called BMP to maintain them. Although the progenitor cells present in the lymph gland are believed to behave like vertebrate stem cells, it is not clear whether fruit flies also have groups of HSCs. Dey et al. studied the fates of cells in the lymph glands of fruit fly larvae. The experiments reveal a new group of cells in the lymph gland that behave like vertebrate stem cells and give rise to progenitor cells. Since the newly discovered cells also depend on a niche for their maintenance, Dey et al. named them HSCs. Further experiments show that, like HSCs in vertebrates, the fruit fly HSCs use Dpp (the fruit fly equivalent of BMP) as a niche signal. The next challenge is to use fruit fly HSCs as models to study how the blood develops in vertebrates, and how this is altered in individuals with blood disorders.