Department of Cell and Tissue Biology.
Department of Cell and Tissue Biology; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research; Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
Exp Hematol. 2014 Aug;42(8):717-27. doi: 10.1016/j.exphem.2014.06.002. Epub 2014 Jun 17.
Fish, mice, and humans rely on two coexisting myeloid blood cell systems. One is sustained by hematopoietic progenitor cells, which reside in specialized microenvironments (niches) in hematopoietic organs and give rise to cells of the monocyte lineage. The other system corresponds to the independent lineage of self-renewing tissue macrophages, which colonize organs during embryonic development and are maintained during later life by proliferation in local tissue microenvironments. However, little is known about the nature of these microenvironments and their regulation. Moreover, many vertebrate tissues contain a mix of both tissue-resident and monocyte-derived macrophages, posing a challenge to the study of lineage-specific regulatory mechanisms and function. This review highlights how research in the simple model organism Drosophila melanogaster can address many of these outstanding questions in the field. Drawing parallels between hematopoiesis in Drosophila and vertebrates, we illustrate the evolutionary conservation of the two myeloid systems across animal phyla. Much like vertebrates, Drosophila possesses a lineage of self-renewing tissue-resident macrophages, which we refer to as tissue hemocytes, as well as a "definitive" lineage of macrophages that derive from hematopoiesis in the progenitor-based lymph gland. We summarize key findings from Drosophila hematopoiesis that illustrate how local microenvironments, systemic signals, immune challenges, and nervous inputs regulate adaptive responses of tissue-resident macrophages and progenitor-based hematopoiesis to maximize fitness of the animal.
鱼类、小鼠和人类依赖于两种共存的骨髓细胞系统。一种是由造血祖细胞维持的，造血祖细胞存在于造血器官的专门微环境（龛）中，并产生单核细胞谱系的细胞。另一种系统对应于自我更新的组织巨噬细胞的独立谱系，这些细胞在胚胎发育过程中殖民器官，并在以后的生活中通过在局部组织微环境中的增殖来维持。然而，人们对这些微环境的性质及其调节知之甚少。此外，许多脊椎动物组织中既有组织驻留的巨噬细胞，也有单核细胞衍生的巨噬细胞，这给研究谱系特异性调节机制和功能带来了挑战。
这篇综述强调了简单模式生物果蝇中的研究如何能够解决该领域的许多这些悬而未决的问题。通过在果蝇和脊椎动物中的造血作用之间进行类比，我们说明了这两个骨髓系统在动物门之间的进化保守性。与脊椎动物非常相似，果蝇具有自我更新的组织驻留巨噬细胞谱系，我们称之为组织血细胞，以及源自基于祖细胞的淋巴腺造血的“明确”巨噬细胞谱系。我们总结了来自果蝇造血作用的关键发现，这些发现说明了局部微环境、系统信号、免疫挑战和神经输入如何调节组织驻留巨噬细胞和基于祖细胞的造血作用的适应性反应，以最大限度地提高动物的适应性。
