GSE239582 Single Cell Transcriptomics identifies a WNT7A-FZD5 Signaling Axis that maintains Fallopian Tube Stem Cells in Patient-derived Organoids [scRNA-seq]

Contributors : Abdulkhaliq Alsaadi ; Zhiyuan Hu ; Mara Artibani ; Francesca Silvestri ; Ahmed AhmedSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensDespite its significance to reproduction, fertility, sexually transmitted infections and various pathologies, the fallopian tube (FT) is relatively understudied. Strong evidence points to the FT as the tissue-of-origin of high grade serous ovarian cancer (HGSOC), the most fatal gynaecological malignancy. HGSOC precursor lesions arise specifically in the distal FT (fimbria) which is reported to be enriched in stem-like cells. Investigation of the role of FT stem cells in health and disease has been hampered by a lack of characterization of FT stem cells and lack of models that recapitulate stem cell renewal and differentiation in vitro. Using optimized organoid culture conditions to address these limitations, we found that FT stem cell renewal is highly dependent on WNT/ β-catenin signaling and engineered endogenous WNT/β-catenin signaling reporter organoids to biomark, isolate and characterize putative FT stem cells. Using functional approaches as well as bulk and single cell transcriptomic analyses, we show that an endogenous hormonally-regulated WNT7A-FZD5 sign aling axis is critical for self-renewal of human FT stem cells, and that WNT/β-catenin pathway-activated cells form a distinct transcriptomic cluster of FT cells enriched in ECM remodelling and integrin signaling pathways. In ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research