EKLF/KLF1 expression defines a unique macrophage subset during mouse erythropoiesis.
EKLF/KLF1 expression defines a unique macrophage subset during mouse erythropoiesis.
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DOI：
10.7554/elife.61070
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发表时间：
2021-02-11
期刊：
影响因子：
7.7
通讯作者：
Bieker JJ
中科院分区：
文献类型：
--
作者：
Mukherjee K;Xue L;Planutis A;Gnanapragasam MN;Chess A;Bieker JJ
成红细胞岛是一个特殊的生态位，包含一个中央巨噬细胞，周围是处于不同成熟阶段的红系细胞。然而，由于巨噬细胞的异质性，确定岛巨噬细胞中精确的遗传和转录控制机制仍然很困难。使用无偏的全球测序和定向遗传方法专注于早期哺乳动物的发展，我们发现，胎肝巨噬细胞表现出独特的表达签名，区分他们从红细胞和成人巨噬细胞。红系Krüppel样因子（EKLF）/KLF 1在这种身份中的重要性通过EKLF-/-和EKLF标记的巨噬细胞中的表达分析显示。单细胞序列分析简化了异质性，并确定了对EKLF依赖性巨噬细胞功能和新型细胞表面生物标志物重要的基因簇。值得注意的是，这组单一的巨噬细胞岛细胞在胚胎发生过程中短暂出现。总之，这些研究提供了一个详细的观点，EKLF在建立动态基因表达网络内成红细胞岛屿在发育中的胚胎的重要性，并提供了有效的隔离手段。
Erythroblastic islands are a specialized niche that contain a central macrophage surrounded by erythroid cells at various stages of maturation. However, identifying the precise genetic and transcriptional control mechanisms in the island macrophage remains difficult due to macrophage heterogeneity. Using unbiased global sequencing and directed genetic approaches focused on early mammalian development, we find that fetal liver macrophages exhibit a unique expression signature that differentiates them from erythroid and adult macrophage cells. The importance of erythroid Krüppel-like factor (EKLF)/KLF1 in this identity is shown by expression analyses in EKLF-/- and in EKLF-marked macrophage cells. Single-cell sequence analysis simplifies heterogeneity and identifies clusters of genes important for EKLF-dependent macrophage function and novel cell surface biomarkers. Remarkably, this singular set of macrophage island cells appears transiently during embryogenesis. Together, these studies provide a detailed perspective on the importance of EKLF in the establishment of the dynamic gene expression network within erythroblastic islands in the developing embryo and provide the means for their efficient isolation.