Stem cells have the ability to self-renew and differentiate. The present project investigated what happens in a stem cell as it differentiates to enable it to switch fate. The Drosophila testis model contains a niche, known as the hub that provides self- renewal signals and supports two stem cell populations, somatic cyst stem cells (CySCs) and germline stem cells (GSCs). Differentiation is considered a passive process, due to a lack of self-renewal signals, once stem cells exit the niche. Previous research in GSCs and haematopoeitic stem cells (HSCs) shows that translation rates increase in differentiating cells and that the increase is necessary for differentiation to occur. Other research also shows that differentiation in the cyst lineage is regulated by increasing PI3K/Tor pathway activity, of which translation is a known target. Translation is largely regulated at the initiation stage and can be initiated in both a cap-dependent and cap-independent manner. Cap-dependent translation requires the binding of eukaryotic initiation factor complex F (eIF4F) to the m7G 5’ cap of an mRNA strand, to recruit ribosomal subunits and initiate translation. Cap-independent methods, such as Internal ribosomal entry site (IRES)-associated translation rely on internal structures to recruit the ribosome independently. Initiation factors such as eIF3 and eIF2 are used in both. To test the role of translation initiation in CySC maintenance and differentiation, I conducted a screen to knock down translation initiation factors by RNAi. Strikingly, different initiation factors had different requirements during CySC differentiation: while knockdown of components of the cap-binding eIF4F complex led to a loss of self-renewal, knockdown of other translation initiation factors led to a lack of differentiation. These results indicate that cap-dependent initiation is required for CySC self-renewal, but dispensable for differentiation and suggest that initiation modes switch during differentiation.
|Date of Award||23 Jan 2019|
- The University of Bristol
|Supervisor||Paul B Martin (Supervisor) & Marc Amoyel (Supervisor)|