WEHI PhD Completion Seminar hosted by Associate Professor Rhys Allan

Quinn Stacpoole
PhD Student – Allan Laboratory, Immunology division, WEHI

Multi-omic gene regulatory networks informed by 3D chromatin architecture reveal insights into hematopoietic stem cell ageing

Davis Auditorium

Join via TEAMS

Including Q&A session      

Hematopoietic stem cells (HSCs) are responsible for continually replenishing the blood system with mature cells, ensuring immune competence and tissue homeostasis. However, during ageing, HSCs have reduced regenerative potential, skewed differentiation toward the myeloid lineage, and heightened susceptibility to clonal expansions and malignancies. Recent studies have illuminated the role of three-dimensional (3D) genome architecture as an additional, critical layer of stem cell regulation. Techniques such as Hi-C can capture how chromosomes fold within the nucleus, revealing interactions between genes and their regulatory elements.

During my PhD project, I examined the 3D genome organisation of young versus aged murine HSCs using Hi-C to map the interactions between chromatin regions and then integrated this with gene expression and chromatin accessibility data to build chromatin-contact-informed gene regulatory networks. Networks were then compared to identify transcription factors (TFs) that drive the network state changes during HSC ageing.

Similar to results in other ageing cell types, the Hi-C analysis of aged vs young HSCs show erosion of topologically associating domain (TAD) boundaries, shifts between active (A) and inactive (B) compartments, and reorganised enhancer-promoter loops, but additionally show enrichment for certain transcription factor motifs, most notably AP-1 motifs. Additionally, differential network analysis predicts key TFs that both drive the ageing state and potentially restore the youthful state.

All welcome!