Characterisation of protein networks driving haematopoietic stem cell fate choice (360G-Wellcome-203763_Z_16_A)

Haematopoietic stem cells (HSCs) are situated at the top of a hierarchy of blood forming cells and are ultimately responsible for the production of all mature blood cell types. HSCs must therefore execute a balance of self-renewal and differentiation divisions to maintain the stem cell population throughout adult life while providing enough cells to meet daily needs. Over the past decades, several HSC subtypes have been described, differing in mature cell type production and self-renewal durability. De-regulation of these cell fate choices in HSCs has been implicated in ageing and tumorigenesis and recent advances in single cell technologies have allowed greater insight into transcriptional changes driving these decisions. However, little is known about how well these profiles correspond to the proteome of HSCs and we therefore aim to construct a comprehensive protein network for HSC subtypes in order to identify key proteins involved in HSC self-renewal. The importance of candidate self-renewal regulators will be assessed by both in vitro and in vivo methods. A more complete understanding of HSC self-renewal would lead the way for more effective in vitro expansion of HSCs for research and future clinical applications such as gene therapy and bone marrow cell transplantation.