Understanding the contribution of developmentally distinct neutrophils to the developing haemato-immune system

Park, Y

Thesis

Understanding the contribution of developmentally distinct neutrophils to the developing haemato-immune system

Abstract:: 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.

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.

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Cite

Cite this record

APA Style

Park, Y. (2023). Understanding the contribution of developmentally distinct neutrophils to the developing haemato-immune system [PhD thesis]. University of Oxford.

MLA Style

Park, Y. Understanding the Contribution of Developmentally Distinct Neutrophils to the Developing Haemato-Immune System. University of Oxford, 2023.

Chicago Style

Park, Y. 2023. “Understanding the Contribution of Developmentally Distinct Neutrophils to the Developing Haemato-Immune System.” PhD thesis, University of Oxford.
Share
Print