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Nov 08, 2019

RPG Seminar Series (Speaker: Miss LEUNG Bernice King-wing / Mr. WENG Mingxi)

Date: Friday, 8 November 2019

Venue: Seminar Room 4, G/F
Laboratory Block, Faculty of Medicine Building
21 Sassoon Road, Hong Kong

Time: 5:00 p.m.

Title: The Roles of Irx3 and Irx5 in mouse cochlear epithelial cell patterning and differentiation
Speaker: Miss LEUNG Bernice King-wing (MPhil candidate)

Irx3 and Irx5 are transcription factors belonging to the Iroquois (Irx) gene family cluster B that are known to cooperate in various developmental processes. Although the Iroquois genes are expressed within the chick inner ear, the particular roles of Irx3 and Irx5 in cochlear epithelial development remain unknown. Therefore, cochlear phenotypes of mutant mice lines of Irx3TauLacZ, Irx5EGFP/EGFP, Irx3-/-Irx5EGFP/EGFP, and Emx2Cre; Irx3floxed/floxedIrx5EGFP/EGFP were studied. Cochlear morphogenesis, cell patterning, and differentiation were largely affected in both conditional and double mutants while single mutants only depicted mild phenotypes. Irx3 and Irx5 largely affects the Sox2 positive prosensory portion and surrounding nonsensory structures of the greater epithelial ridge and lesser epithelial ridge, or outer sulcus, up until postnatal stages. Other nonsensory structures continue to develop normally in the absence of Irx3 and Irx5. These results indicate that Irx3 and Irx5 play an important role in the development of the ventral cochlear epithelium.

Title: Generation of induced neural stem cells by artificially evolved transcription factors
Speaker: Mr. WENG Mingxi (PhD candidate)

To date there are many ways to change the fate of cells and to reprogram a cell into a different lineage, e.g. cocktails of transcription factors. In this study we apply previously gained structural knowledge and prominent cancer mutations within the Sox factors to create artificially evolved transcription factors (eTFs) with enhanced capabilities for transdifferentiation. To benchmark the enhanced efficiency, we used a protocol of directly conversion of mouse somatic cells to induced neural stem cells (iNSCs) and successfully identified eSox variants outperforming the wild-type factors. iNSC generated by eSox factors could be expanded stably and were able to differentiate into neurons and astrocytes in vitro. Subsequently, we will translate our knowledge to the human system, to improve the generation of human iNSCs and test their functionality in animal models and brain organoids. This will provide cell sources for research and therapy of neurodegenerative diseases.