의생명시스템학부

제목: Integrative single cell analysis identifies key genes responsible for disease development

내용:

In the first part of this talk, single cell analysis results of kidney disease will be presented. Cell type-specific differential expression analysis identified proximal tubule cells (PT cells) as the key vulnerable cell type in diseased kidneys. Through unbiased cell trajectory analyses, we show that PT cell differentiation state is altered in disease state. Lipid metabolism (fatty acid oxidation and oxidative phosphorylation) in PT cells showed the strongest and reproducible association with PT cells state. The coupling of cell state and metabolism is established by nuclear receptors such as PPARA and ESRRA that not only control cellular metabolism but also the expression of PT cell-specific genes in mice and patient samples. In the second part of this talk, single cell analysis results of thyroid cancer will be presented. In this study, we provided integrated single-cell resolution research in de-differentiation process of thyroid cancer with 46,205 cells. Development trajectory and regulatory network analysis indicated that ATC derived from a small subset of PTC cells, and CREB3L1 expression may determine cell fate of thyroid cancer, which validated by integrated copy number alteration (CNA) profiles and immunofluorescence. ChIP-seq profile and single-cell transcriptome identified that multiple genes in de-differentiation-related pathways (e.g., EMT) were involved as the downstream targets of CREB3L1, increased expression of which can thus predict higher risk of relapse and poor treatment outcome of thyroid cancer. Collectively, these data provided insightful view in de-differentiation of thyroid cancer in alteration of microenvironment and tumoral genomics.