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Sara Tomei – Immunology division

16/08/2023 1:00 pm - 16/08/2023 2:00 pm
Location
Davis Auditorium

WEHI Wednesday Seminar hosted by Associate Professor Shalin Naik
 

Sara Tomei
PhD Student – Naik Laboratory, Immunology division – Infection, Inflammation & Immunity Theme, WEHI 
(this is a PhD Completion seminar)

Haematopoiesis at a clonal level using novel barcoding technologies

 

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session
 

 

Haematopoiesis is a highly regulated process in which hematopoietic stem and progenitor cells (HSPCs) divide and differentiate to in order to generate all mature blood cell types. The advent of single-cell technologies (single cell RNA-seq and clonal barcoding strategies) has revealed a great deal of heterogeneity in both the transcriptional profiles and clonal lineage potential of different HSPC populations. However, few studies have investigated haematopoiesis at a clonal level in in relevant human in vitro models, or in mice in a native unperturbed setting i.e. clonal lineage tracing models that do not rely on the potentially artefactual settings of transplantation into irradiated hosts. To tackle these challenges, the Naik lab has developed novel tools and approaches in both these domains to answer questions regarding the contribution of HSCs at the clonal level for overall blood production in the organism, how HSCs behave with regards to quiescence versus active contribution, and the underlying molecular signatures governing HSPC fate potential.

 

In her PhD, Sara employs innovative barcoding technologies to examine HSC behaviour in both murine and human contexts. Firstly, she utilizes the Loxcode mouse, an in vivo murine barcoding model, to assess the clonal contribution of HSPCs to native haematopoiesis. Two conflicting models exist regarding whether HSCs contribute to adult haematopoiesis or only exist in a quiescent state where downstream multipotent progenitors are instead the primary contributor to haematopoiesis. Here, Sara tracks the clonal relatedness of seven different HSPC populations over a 32-week period under both steady-state conditions, and G-CSF-mediated emergency haematopoiesis to understand and compare HSCs contribution in both systems.

Secondly, Sara employs optimised in vitro multilineage culture system that can generate multiple  cell types. Coupled with SPLINTR lentiviral barcoding, she investigates the molecular mechanisms by which human HSPCs contribute to haematopoiesis. Through this approach, she identifies genes expressed in HSPCs that correlate with lineage commitment and bias to different mature populations as well as the kinetics of that production.

 

Overall, Sara’s research has helped unravel the hematopoietic process and identify key genes associated with HSC fate determination. This knowledge will help provide insight into genes crucial for the production of specific immune cell types, which may translate to novel opportunities for manipulating human HSCs to enhance or inhibit the production of desired cell populations in the clinic for cancer, immune deficiency and immunotherapy.

 

All welcome!

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