Autophagy regulates the maturation of hematopoietic precursors in the embryo
Abstract An understanding of the mechanisms regulating embryonic hematopoietic stem cell (HSC) development would facilitate their regeneration. The aorta-gonad-mesonephros region is the site for HSC production from hemogenic endothelial cells (HEC). While several distinct regulators are involved in...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46453-y |
| _version_ | 1827315929297453056 |
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| author | Yumin Liu Linjuan Shi Yifan Chen Sifan Luo Yuehang Chen Hongtian Chen Wenlang Lan Xun Lu Zhan Cao Zehua Ye Jinping Li Bo Yu Elaine Dzierzak Zhuan Li |
| author_facet | Yumin Liu Linjuan Shi Yifan Chen Sifan Luo Yuehang Chen Hongtian Chen Wenlang Lan Xun Lu Zhan Cao Zehua Ye Jinping Li Bo Yu Elaine Dzierzak Zhuan Li |
| author_sort | Yumin Liu |
| collection | DOAJ |
| description | Abstract An understanding of the mechanisms regulating embryonic hematopoietic stem cell (HSC) development would facilitate their regeneration. The aorta-gonad-mesonephros region is the site for HSC production from hemogenic endothelial cells (HEC). While several distinct regulators are involved in this process, it is not yet known whether macroautophagy (autophagy) plays a role in hematopoiesis in the pre-liver stage. Here, we show that different states of autophagy exist in hematopoietic precursors and correlate with hematopoietic potential based on the LC3-RFP-EGFP mouse model. Deficiency of autophagy-related gene 5 (Atg5) specifically in endothelial cells disrupts endothelial to hematopoietic transition (EHT), by blocking the autophagic process. Using combined approaches, including single-cell RNA-sequencing (scRNA-seq), we have confirmed that Atg5 deletion interrupts developmental temporal order of EHT to further affect the pre-HSC I maturation, and that autophagy influences hemogenic potential of HEC and the formation of pre-HSC I likely via the nucleolin pathway. These findings demonstrate a role for autophagy in the formation/maturation of hematopoietic precursors. |
| first_indexed | 2024-04-24T23:05:12Z |
| format | Article |
| id | doaj.art-b0404ef03301401caf800eeb999f01ab |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T23:05:12Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-b0404ef03301401caf800eeb999f01ab2024-03-17T12:31:09ZengNature PortfolioNature Communications2041-17232024-03-0115111710.1038/s41467-024-46453-yAutophagy regulates the maturation of hematopoietic precursors in the embryoYumin Liu0Linjuan Shi1Yifan Chen2Sifan Luo3Yuehang Chen4Hongtian Chen5Wenlang Lan6Xun Lu7Zhan Cao8Zehua Ye9Jinping Li10Bo Yu11Elaine Dzierzak12Zhuan Li13Key Laboratory of Functional Proteomics of Guangdong Province, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical UniversityKey Laboratory of Functional Proteomics of Guangdong Province, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical UniversityKey Laboratory of Functional Proteomics of Guangdong Province, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical UniversityKey Laboratory of Functional Proteomics of Guangdong Province, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical UniversityKey Laboratory of Functional Proteomics of Guangdong Province, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical UniversityKey Laboratory of Functional Proteomics of Guangdong Province, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical UniversityKey Laboratory of Functional Proteomics of Guangdong Province, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical UniversityKey Laboratory of Functional Proteomics of Guangdong Province, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical UniversityKey Laboratory of Functional Proteomics of Guangdong Province, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical UniversityKey Laboratory of Functional Proteomics of Guangdong Province, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical UniversityKey Laboratory of Functional Proteomics of Guangdong Province, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical UniversityInstitute of Hematology, School of Medicine, Jinan UniversityCentre for Inflammation Research, The University of EdinburghKey Laboratory of Functional Proteomics of Guangdong Province, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical UniversityAbstract An understanding of the mechanisms regulating embryonic hematopoietic stem cell (HSC) development would facilitate their regeneration. The aorta-gonad-mesonephros region is the site for HSC production from hemogenic endothelial cells (HEC). While several distinct regulators are involved in this process, it is not yet known whether macroautophagy (autophagy) plays a role in hematopoiesis in the pre-liver stage. Here, we show that different states of autophagy exist in hematopoietic precursors and correlate with hematopoietic potential based on the LC3-RFP-EGFP mouse model. Deficiency of autophagy-related gene 5 (Atg5) specifically in endothelial cells disrupts endothelial to hematopoietic transition (EHT), by blocking the autophagic process. Using combined approaches, including single-cell RNA-sequencing (scRNA-seq), we have confirmed that Atg5 deletion interrupts developmental temporal order of EHT to further affect the pre-HSC I maturation, and that autophagy influences hemogenic potential of HEC and the formation of pre-HSC I likely via the nucleolin pathway. These findings demonstrate a role for autophagy in the formation/maturation of hematopoietic precursors.https://doi.org/10.1038/s41467-024-46453-y |
| spellingShingle | Yumin Liu Linjuan Shi Yifan Chen Sifan Luo Yuehang Chen Hongtian Chen Wenlang Lan Xun Lu Zhan Cao Zehua Ye Jinping Li Bo Yu Elaine Dzierzak Zhuan Li Autophagy regulates the maturation of hematopoietic precursors in the embryo Nature Communications |
| title | Autophagy regulates the maturation of hematopoietic precursors in the embryo |
| title_full | Autophagy regulates the maturation of hematopoietic precursors in the embryo |
| title_fullStr | Autophagy regulates the maturation of hematopoietic precursors in the embryo |
| title_full_unstemmed | Autophagy regulates the maturation of hematopoietic precursors in the embryo |
| title_short | Autophagy regulates the maturation of hematopoietic precursors in the embryo |
| title_sort | autophagy regulates the maturation of hematopoietic precursors in the embryo |
| url | https://doi.org/10.1038/s41467-024-46453-y |
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