Cebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish

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 () and Yiyue Zhang ()
Additional contact information
Gaofei Li: South China University of Technology
Yicong Sun: South China University of Technology
Immanuel Kwok: A*STAR (Agency for Science, Technology and Research)
Liting Yang: Southern Medical University
Wanying Wen: South China University of Technology
Peixian Huang: South China University of Technology
Mei Wu: South China University of Technology
Jing Li: South China University of Technology
Zhibin Huang: South China University of Technology
Zhaoyuan Liu: Shanghai JiaoTong University School of Medicine
Shuai He: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Wan Peng: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Jin-Xin Bei: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Florent Ginhoux: A*STAR (Agency for Science, Technology and Research)
Lai Guan Ng: A*STAR (Agency for Science, Technology and Research)
Yiyue Zhang: South China University of Technology

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-45029-0

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