Understanding adult human hematopoiesis in ageing and chemotherapy (360G-Wellcome-222382_Z_21_Z)

The resilience of the human hematopoietic system declines with age as it becomes more susceptible to age-related disorders or malignancies, produces lower blood counts and is less capable of fighting off infections. When subjected to chemotherapy, it can be severely challenged, but cell counts will usually recover in 2 to 3 weeks. However, in older patients, the recovery can be slower, and individuals over the age of 75 are unable to tolerate more intense regimens. In my project, I will compare and contrast the clonal composition and functional characteristics of hematopoietic cells from patients before and after receiving chemotherapy. To achieve this, blood samples of consenting patients between the ages of 40 and 90 will be obtained before and after their treatment, and I will grow single-cell derived colonies and then profile their DNA and single-cell RNA. This will allow me to measure how perturbation of the systemic environment affects the clonal composition of blood, how the proliferative capacities of cells are affected and what functional changes occur in their transcriptomes. This study will help us understand to what extent the fitness of hematopoietic stem cells is environment-dependent and how ageing affects the recovery time after chemotherapy.