Cebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish
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 la...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45029-0 |
| _version_ | 1797276390820675584 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Gaofei Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T15:27:37Z |
| format | Article |
| id | doaj.art-3fea63b6b24a49bba081a7c7051025dd |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T15:27:37Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-3fea63b6b24a49bba081a7c7051025dd2024-03-05T16:36:00ZengNature PortfolioNature Communications2041-17232024-01-0115111510.1038/s41467-024-45029-0Cebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafishGaofei Li0Yicong Sun1Immanuel Kwok2Liting Yang3Wanying Wen4Peixian Huang5Mei Wu6Jing Li7Zhibin Huang8Zhaoyuan Liu9Shuai He10Wan Peng11Jin-Xin Bei12Florent Ginhoux13Lai Guan Ng14Yiyue Zhang15Department of Hematology, the Second Affiliated Hospital, School of Medicine, South China University of TechnologyInnovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologySingapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research)Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical UniversityInnovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyInnovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyInnovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyInnovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyInnovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyShanghai Institute of Immunology, Shanghai JiaoTong University School of MedicineSun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineSingapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research)Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research)Department of Hematology, the Second Affiliated Hospital, School of Medicine, South China University of TechnologyAbstract 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.https://doi.org/10.1038/s41467-024-45029-0 |
| spellingShingle | 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 Cebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish Nature Communications |
| title | Cebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish |
| title_full | Cebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish |
| title_fullStr | Cebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish |
| title_full_unstemmed | Cebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish |
| title_short | Cebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish |
| title_sort | cebp1 and cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish |
| url | https://doi.org/10.1038/s41467-024-45029-0 |
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