Tissue Repair Postgraduate Training Programme

New mechanism to suppress inflammation in hematopoietic stem cells identified by Tissue Repair PhD student Chris Mapperley

Study by Mapperley et al identifies mRNA m6A reader YTHDF2 as suppressor of inflammatory pathways in hematopoietic stem cells (HSC) and highlights the significance of m6A in long-term HSC maintenance.

Chris Mapperley, a final year Wellcome Trust Tissue Repair PhD student at the Centre for Regenerative Medicine working in the O’Carroll lab, reports on a new mechanism to suppress inflammation in stem cells, maintaining their fitness and function.

Chris has been researching the role of RNA binding protein YTHDF2 in haematopoietic stem cells (HSC). YTHDF2 recognises methylated mRNA and directs its degradation. Targeting YTHDF2 can expand normal stem cells and eradicate leukaemia.

Setting out to determine whether stem cell expansion could be maintained without deleterious effects, Chris identified that in HSCs, targeted degradation of inflammatory mRNA transcripts by YTHDF2 is essential to avoid chronic stem cell immune activation and eventual exhaustion. This has identified a new role for RNA biology in stem cells and an essential therapeutic window for targeting of YTHDF2.

The study is published in the Journal of Experimental Medicine.

Mapperley, C., et al.  The mRNA m6A reader YTHDF2 suppresses proinflammatory pathways and sustains hematopoietic stem cell function J Exp Med (2021) 218 (3): e20200829.