Understanding the contribution of developmentally distinct neutrophils to the developing haemato-immune system
<p>Neutrophils play a critical role in host defense, especially in neonates whose immune systems are not yet fully developed. Neutrophils originate from at least two origins: yolk sac-derived erythromyeloid progenitors (EMPs) and aorta-derived hematopoietic stem cells (HSCs). In zebrafish, dev...
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| Format: | Thesis |
| Language: | English |
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2023
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| _version_ | 1811139843658350592 |
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| author | Park, Y |
| author2 | De bruijn, M |
| author_facet | De bruijn, M Park, Y |
| author_sort | Park, Y |
| collection | OXFORD |
| description | <p>Neutrophils play a critical role in host defense, especially in neonates whose immune systems are not yet fully developed. Neutrophils originate from at least two origins: yolk sac-derived erythromyeloid progenitors (EMPs) and aorta-derived hematopoietic stem cells (HSCs). In zebrafish, developmentally discrete neutrophil populations are associated with different functions. In addition, our transcriptomic analysis of neutrophils isolated from E18.5 fetuses has inferred three mature, yet functionally distinct, subsets, with gene set enrichment analysis indicating conventional, anti-viral and regulatory functions respectively among bone marrow neutrophils, leading us to hypothesize that mammalian neutrophils from distinct developmental origins may also have discrete functions and/or gestational stage-specific contributions to the hematopoietic system.</p>
<p>To explore this, we have used lineage tracing to establish a spatiotemporal map of EMP- and HSC-derived neutrophils during mouse fetal and neonatal development. We discovered dynamic shifts perinatally in the contribution of developmentally distinct neutrophils, with specific changes in the precursor subset in liver, spleen and bone marrow. Interestingly, analyses of E18.5 EMP- and HSC-lineage-traced neutrophils expressed different gene signatures that suggest distinct functions for neutrophils derived from these developmental origins. Gene regulatory network analysis using SCENIC revealed lineagespecific motifs and TFs. Functional assays of E18.5 EMP- and HSC-derived neutrophils revealed similar phagocytic capacity but suggested an enhanced response of HSC-derived neutrophils to ROS signaling. These studies yield basic insights into early-life neutrophil biology and serve as a benchmark for future translational studies.</p> |
| first_indexed | 2024-09-25T04:12:32Z |
| format | Thesis |
| id | oxford-uuid:a29e7edc-98e9-4507-ade6-9f2138283078 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:12:32Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | oxford-uuid:a29e7edc-98e9-4507-ade6-9f21382830782024-06-25T09:54:12ZUnderstanding the contribution of developmentally distinct neutrophils to the developing haemato-immune systemThesishttp://purl.org/coar/resource_type/c_db06uuid:a29e7edc-98e9-4507-ade6-9f2138283078ImmunologyPediatricsDevelopmental biologyHematologyEnglishHyrax Deposit2023Park, YDe bruijn, MRoberts, IRode, C<p>Neutrophils play a critical role in host defense, especially in neonates whose immune systems are not yet fully developed. Neutrophils originate from at least two origins: yolk sac-derived erythromyeloid progenitors (EMPs) and aorta-derived hematopoietic stem cells (HSCs). In zebrafish, developmentally discrete neutrophil populations are associated with different functions. In addition, our transcriptomic analysis of neutrophils isolated from E18.5 fetuses has inferred three mature, yet functionally distinct, subsets, with gene set enrichment analysis indicating conventional, anti-viral and regulatory functions respectively among bone marrow neutrophils, leading us to hypothesize that mammalian neutrophils from distinct developmental origins may also have discrete functions and/or gestational stage-specific contributions to the hematopoietic system.</p> <p>To explore this, we have used lineage tracing to establish a spatiotemporal map of EMP- and HSC-derived neutrophils during mouse fetal and neonatal development. We discovered dynamic shifts perinatally in the contribution of developmentally distinct neutrophils, with specific changes in the precursor subset in liver, spleen and bone marrow. Interestingly, analyses of E18.5 EMP- and HSC-lineage-traced neutrophils expressed different gene signatures that suggest distinct functions for neutrophils derived from these developmental origins. Gene regulatory network analysis using SCENIC revealed lineagespecific motifs and TFs. Functional assays of E18.5 EMP- and HSC-derived neutrophils revealed similar phagocytic capacity but suggested an enhanced response of HSC-derived neutrophils to ROS signaling. These studies yield basic insights into early-life neutrophil biology and serve as a benchmark for future translational studies.</p> |
| spellingShingle | Immunology Pediatrics Developmental biology Hematology Park, Y Understanding the contribution of developmentally distinct neutrophils to the developing haemato-immune system |
| title | Understanding the contribution of developmentally distinct neutrophils to the developing haemato-immune system |
| title_full | Understanding the contribution of developmentally distinct neutrophils to the developing haemato-immune system |
| title_fullStr | Understanding the contribution of developmentally distinct neutrophils to the developing haemato-immune system |
| title_full_unstemmed | Understanding the contribution of developmentally distinct neutrophils to the developing haemato-immune system |
| title_short | Understanding the contribution of developmentally distinct neutrophils to the developing haemato-immune system |
| title_sort | understanding the contribution of developmentally distinct neutrophils to the developing haemato immune system |
| topic | Immunology Pediatrics Developmental biology Hematology |
| work_keys_str_mv | AT parky understandingthecontributionofdevelopmentallydistinctneutrophilstothedevelopinghaematoimmunesystem |