Elaine Fuchs (The Rockefeller University, USA HHMI Investigator)
“Transition of Normal Epithelia to Cancer”
Webpage http://www.rockefeller.edu/research/faculty/labheads/ElaineFuchs/#content
- a student of Howard Green, who just passed away several mo ago
- The foundation of embryonic stem cell culture to come in 1980s burn therapy
- quiescent stem cell and primed stem cells awaiting for activation
- Hair follicle stem cells
- BMP signaling governs stem cell quiescence
- Lossof Foxc1 abrogated stem cell quiescence
- Stem cell specific bind to 400 large open chromatin domains called super-enhancer
- SOX 9, BMP
- Epicenters posses the information needed for a gene to get to a niche microenvironment
- in vitro, HF stem cell transcription factors are downregulated by SOX 9 (ref: Adams and Yang and Fuchs)
- SCC cancers
- Tumor initiating SCC stem cells
- Super-enhancer SCC (eLife 2015 Yang ETS family transcriptional regulators drive chromatin dynamics and malignancy in squamous cell carcinomas.)
- Activated ETS2 (ref: Oshimori and Fuchs Cell 2015 TGF-β promotes heterogeneity and drug resistance in squamous cell carcinoma)
- TGFb responsiveness in primary tumors
- HRAS v12
- Sox9 is shared in both key HF SC genes and key SCC SC genes
- ETS2 or ELK3 (ref: Foulds et al)
- Genetic lineage tracing (developed by Hans Clever Group Identification of stem cells in small intestine and colon by marker gene Lgr5.)
- Some cells have TGFBR receive TGFb
- TME heterogeneity determine stem cell variations (TGF-β Promotes Heterogeneity and Drug Resistance in Squamous Cell Carcinoma)
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From Ming-Han
From Ming-Han
- Main model: hair cells
- Main question: (1) how grow; how not grow; why go into white hair?
- find stem cells (fast grow (TGFB-); grow fast but not increase. (slow (TGFB+); grow slow near vessel)
- Use lineage tracing techniques to track the fate of the cells
- Strategy
- Use lentivirus to infect d5 embryo: reason: at this stage the skin layer is monolayer in embryo.
- TGF-b responding stem cells have resistant to Cisplatin.
- For epithelial cells
- BSA+cisplatin: all dead
- TGFb+Cisplatin: not death; become flatten, can use for drug screening? (TGFb is important for microenvironment and vessel formation)
- @@Read : lineage tracing techniques!! Can trace the fate of the cells!! Shimori and Fuches Cell 2015