The role of Tet in the drosophila ovarian germline stem cell differentiation niche

Abstract

After transcription, RNA may undergo various chemical modifications, such as m6A, 5mC, 5hmC. Tet family proteins can catalyze 5mC into 5hmC in both DNA and RNA. Tet and RNA 5hmC modifications have been reported to be involved in organ developmental, tissue homeostasis and stem cell differentiation, but the underlying mechanisms remain largely unclear. The Drosophila ovary germline stem cell (GSC) is an excellent model for studying stem cell self-renewal and differentiation. Our previous study found that Tet is specifically enriched in the Drosophila GSC differentiation niche. Overexpression of Tet in the niche can cause defects in ovarian development, such as decreased number of GSCs, increased number of CBs, and reduced number of egg chambers, indicating abnormal self-renewal and differentiation of GSCs. From previous mass spectrometry of our lab, Tet was found to bind to RNA splicing factors. Then co-immunoprecipitation experiments prove that Tet protein physically interacts with splicing factors by its C terminal domain. Through genetic screening, I found that knocking down RNA splicing factors significantly rescues the developmental abnormalities caused by Tet overexpression and knockdown of Tet enhances the GSC progeny differentiation defects induced by the knockdown of RNA splicing factors, suggesting that Tet is genetically associated RNA splicing factors to modulate GSC progeny differentiation. Furthermore, RNAseq results showed that Tet overexpression promote RNA splicing and exon skipping. Taken together, in this thesis, our results suggest that Tet may be involved in mRNA splicing. Our findings provide a new function of Tet in regulating stem cell self-renewal and differentiation.

Date of Award	2023
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Ting XIE (Supervisor)