Department of Biological Sciences, George Washington University, Washington, DC, 20052, USA.
Department of Biological Sciences, George Washington University, Washington, DC, 20052, USA.
Dev Comp Immunol. 2020 Dec;113:103798. doi: 10.1016/j.dci.2020.103798. Epub 2020 Jul 31.
The differentiation of distinct leukocyte subsets is governed by lineage-specific growth factors that elicit disparate expression of transcription factors and markers by the developing cell populations. For example, macrophages (Mφs) and granulocytes (Grns) arise from common granulocyte-macrophage progenitors in response to distinct myeloid growth factors. In turn, myelopoiesis of the Xenopus laevis anuran amphibian appears to be unique to other studied vertebrates in several respects while the functional differentiation of amphibian Mφs and Grns from their progenitor cells remains poorly understood. Notably, the expression of colony stimulating factor-1 receptor (CSF-1R) or CSF-3R on granulocyte-macrophage progenitors marks their commitment to Mφ- or Grn-lineages, respectively. CSF-1R is activated by the colony stimulating factor-1 (CSF-1) and interleukin (IL-34) cytokines, resulting in morphologically and functionally distinct Mφ cell types. Conversely, CSF-3R is ligated by CSF-3 in a process indispensable for granulopoiesis. Presently, we explore the relationships between X. laevis CSF-1-Mφs, IL-34-Mφs and CSF-3-Grns by examining their expression of key lineage-specific transcription factor and myeloid marker genes as well as their enzymology. Our findings suggest that while the CSF-1- and IL-34-Mφs share some commonalities, the IL-34-Mφs possess transcriptional patterns more akin to the CSF-3-Grns. IL-34-Mφs also possess robust expression of dendritic cell-associated transcription factors and surface marker genes, further underlining the difference between this cell type and the CSF-1-derived frog Mφ subset. Moreover, the three myeloid populations differ in their respective tartrate-resistant acid phosphatase, specific- and non-specific esterase activity. Together, this work grants new insights into the developmental relatedness of these three frog myeloid subsets.
不同白细胞亚群的分化受谱系特异性生长因子的控制,这些生长因子通过发育中的细胞群引起不同的转录因子和标志物的表达。例如,巨噬细胞(Mφs)和粒细胞(Grns)来源于共同的粒细胞-巨噬细胞祖细胞,对不同的骨髓生长因子作出反应。反过来,非洲爪蟾的骨髓发生在几个方面似乎是其他研究的脊椎动物所特有的,而两栖动物 Mφs 和 Grns 从其祖细胞的功能分化仍然知之甚少。值得注意的是,集落刺激因子-1 受体(CSF-1R)或集落刺激因子-3 受体(CSF-3R)在粒细胞-巨噬细胞祖细胞上的表达分别标志着它们向 Mφ或 Grn 谱系的定向分化。CSF-1R 被集落刺激因子-1(CSF-1)和白细胞介素(IL-34)细胞因子激活,导致形态和功能上不同的 Mφ细胞类型。相反,CSF-3R 被 CSF-3 配体激活,这一过程对粒细胞发生是不可或缺的。目前,我们通过检查关键的谱系特异性转录因子和髓样标记基因的表达以及它们的酶学特性,来研究非洲爪蟾 CSF-1-Mφs、IL-34-Mφs 和 CSF-3-Grns 之间的关系。我们的研究结果表明,尽管 CSF-1 和 IL-34-Mφs 有一些共同之处,但 IL-34-Mφs 具有更类似于 CSF-3-Grns 的转录模式。IL-34-Mφs 还具有树突状细胞相关转录因子和表面标记基因的强烈表达,进一步强调了这种细胞类型与 CSF-1 衍生的青蛙 Mφ亚群之间的差异。此外,这三种髓样细胞群体在各自的抗酒石酸酸性磷酸酶、特异性和非特异性酯酶活性方面存在差异。总的来说,这项工作深入了解了这三种青蛙髓样亚群的发育相关性。