Cebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish

Cebp1 和 Cebpβ 转录轴控制斑马鱼嗜酸性粒细胞的生成

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作者:Gaofei Li # ,Yicong Sun # ,Immanuel Kwok ,Liting Yang ,Wanying Wen ,Peixian Huang ,Mei Wu ,Jing Li ,Zhibin Huang ,Zhaoyuan Liu ,Shuai He ,Wan Peng ,Jin-Xin Bei ,Florent Ginhoux ,Lai Guan Ng ,Yiyue Zhang

Abstract

Eosinophils are a group of granulocytes well known for their capacity to protect the host from parasites and regulate immune function. Diverse biological roles for eosinophils have been increasingly identified, but the developmental pattern and regulation of the eosinophil lineage remain largely unknown. Herein, we utilize the zebrafish model to analyze eosinophilic cell differentiation, distribution, and regulation. By identifying eslec as an eosinophil lineage-specific marker, we establish a Tg(eslec:eGFP) reporter line, which specifically labeled cells of the eosinophil lineage from early life through adulthood. Spatial-temporal analysis of eslec+ cells demonstrates their organ distribution from larval stage to adulthood. By single-cell RNA-Seq analysis, we decipher the eosinophil lineage cells from lineage-committed progenitors to mature eosinophils. Through further genetic analysis, we demonstrate the role of Cebp1 in balancing neutrophil and eosinophil lineages, and a Cebp1-Cebpβ transcriptional axis that regulates the commitment and differentiation of the eosinophil lineage. Cross-species functional comparisons reveals that zebrafish Cebp1 is the functional orthologue of human C/EBPεP27 in suppressing eosinophilopoiesis. Our study characterizes eosinophil development in multiple dimensions including spatial-temporal patterns, expression profiles, and genetic regulators, providing for a better understanding of eosinophilopoiesis.

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