Date: Wednesday, 31 March 2021

Venue: Cheung Kung Hai Lecture Theatre 2, G/F, William M.W. Mong Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong [Mixed mode: Face-to-Face and Zoom]

Time: 5:00 p.m. - 6:00 p.m.

Zoom Link: https://hku.zoom.us/j/96798236863?pwd=L2lybEQ5aUVsT1RJRmpON0JjTmJvUT09

Meeting ID: 967 9823 6863

Password: 765476

Time: 5:00 p.m.
Speaker: Dr. Lei Zhou (Post-doctoral Fellow)
Primary Supervisor: Dr. SKY Ma
Presentation Title: Lineage traci006Eg and single-cell analysis reveal Prom1+ transit-amplifying tumor cells and their dynamic cellular transition during liver cancer progression

Background: Our group previously identified Prominin-1 (Prom1)/CD133 as an important liver cancer stem cell marker in human HCC. In this study, we investigate the role, heterogeneity and properties of Prom1+ cells in HCC in intact mouse models.

Design: We performed lineage tracing and genetic ablation at different time points pre- and post-HCC induction. scRNA-seq was carried out to analyze the lineage properties, heterogeneity and dynamics of the traced Prom1+ cells.

Results: Prom1+ cells in HCC mouse models do not originate from Prom1-expressing biliary epithelial cells in the normal adult liver. Labeled Prom1+ HCC cells exhibited increased proliferative ability and tumorigenicity in 3D culture and allotransplantation. Targeted depletion of Prom1+ cells impeded HCC tumor growth. scRNA-seq analysis of resident cells in HCC showed that the Prom1-derived HCC cells were highly heterogeneous, and revealed a dedifferentiation trajectory from pericentral lesions to poorly differentiated HCC cells. HCC cells of the Prom1 lineage possess activated oxidant detoxification, underlying the protective mechanism of cancer progenitor cells transitioning to malignant cells, as well as predicting poor prognosis in human HCC.

Conclusion: Our study combines in vivo lineage tracing and scRNA-seq to reveal the heterogeneity and dynamics of Prom1+ HCC progenitor cells, providing insights into the mechanistic role of malignant liver cancer progenitor cells in HCC progression.

Time: 5:30 p.m. 
Speaker: Dr. Michelle Grace Tsui (Post-doctoral Fellow)
Primary Supervisor: Dr. KM Yao
Presentation Title: Pdzd2, a novel modulator of Hedgehog signaling, is involved in the pathogenesis of Glaucoma
Abstract: Pdzd2 is a multi-PDZ domain containing protein that can be processed to generate the secreted form, sPDZD2 which functions as a signaling molecule. Previous studies showed that Pdzd2 was expressed in Hedgehog (Hh) responsive tissues including, paraxial mesoderm, neural tube and limb bud during early development in mouse. Functional studies showed that sPdzd2 counteracted Hh signaling in the chicken neural tube and cell-based reporter assays. Recently, pull- down assays showed that sPDZD2 was able to interact with Gpr161, an orphan receptor that negatively regulates Hh signaling. Co- overexpression of sPDZD2 and Gpr161 in the chicken neural tube showed enhanced negative effect on Hh signaling suggesting that sPDZD2 modulated Hh signaling via Gpr161. 

Furthermore, genome-wide association studies of optic disc characteristics identified statistically significant association of a single nucleotide polymorphism (SNP) within PDZD2 with glaucoma endophenotypes. Interestingly, Pdzd2 mutant mice exhibited glaucoma characteristics including elevation in intraocular pressure and vertical cup- disc ratio, providing the first evidence that Pdzd2 is involved in the pathogenesis of glaucoma.

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