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Hui Shi Saw – Immunology division

12/07/2024 3:00 pm - 12/07/2024 4:00 pm
Location
Davis Auditorium

WEHI MPhil Completion Seminar hosted by Professor Shalin Naik

Hui Shi Saw

PhD Student -  Naik Laboratory, Immunology division – Infection, Inflammation & Immunity Theme, WEHI

 

A New Regulator of ‘Stemness’ to Create Dendritic Cell Factories for Immunotherapy

 

 

Davis Auditorium

Join via SLIDO enter code #WEHIphdcompletion

Including Q&A session

Followed by refreshments in Tapestry Lounge

 

 

A promising avenue in cancer immunotherapy is the utilisation of conventional dendritic cell (cDC)-based vaccines due to the antigen-presenting ability of DCs. However, a limitation for their utilisation is the incapability of producing them in large numbers. Through a CRISPR screen, the Naik lab has characterised Bcor, which when deleted led to (1) higher numbers and (2) sustained generation of cDC2s and pDCs in vitro. However, how Bcor regulates DC differentiation and why its deficiency confers such a ‘stemness’ property are unknown.

 

I first characterised DC generation using cultures of Bcor-deficient haematopoietic stem and progenitor cells (HSPCs) from Cre-LoxP mice (BcorKO)  cultured with Flt3L (Flt3L-DC cultures). I confirmed that BcorKO Flt3L-DC culture sustained ≥4x longer than that of wild type (WT). Additionally, when BcorKO common dendritic progenitors (CDPs) were sorted and re-cultured with Flt3L, they differentiated to most DC populations, similar to their WT counterpart. To examine which cell type contributed to higher DC numbers and sustained growth in Flt3L-DC cultures, I determined that CDPs are hyperproliferative when Bcor is absent, implicating this stage in conferring the observed ‘stemness’ phenotype.

 

To decipher the role of Bcor on a transcriptomic level, I compared the differences in gene expression between WT and BcorKO HSPCs cultured in Flt3L at various times to determine which genes are dysregulated in BcorKO thereby conferring the ‘stemness’ property. A selection of these differentially expressed genes will be deleted using CRISPR in the future to identify those that phenocopy the BcorKO stemness property.

 

Overall, this project has characterised for the first time the role of Bcor during DC differentiation at both the cellular and transcriptomic level. This knowledge will be useful for the development of a scalable DC production to bypass the current limitations in DC-based vaccination and improve the treatment of solid cancers.

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