par Eski, Sema Elif 
;Romitti, Mirian ;De Faria Da Fonseca, Barbara ;Gillotay, Pierre ;Costagliola, Sabine ;Singh, Sumeet Pal
Référence Applied Bioinformatics in Life Sciences (3rd edition: 2020-02-13: Leuven, Belgium)
Publication Publié, 2020-02-13
;Romitti, Mirian ;De Faria Da Fonseca, Barbara ;Gillotay, Pierre ;Costagliola, Sabine ;Singh, Sumeet Pal Référence Applied Bioinformatics in Life Sciences (3rd edition: 2020-02-13: Leuven, Belgium)
Publication Publié, 2020-02-13
Poster de conférence
| Résumé : | More than 10 % of the human population suffers from thyroid-related disorders, against which stem-cell derived organoid models provide therapeutic promise. Previous work from our group reported generation of functional thyroid tissue from mouse embryonic stem cells in vitro. However, the efficiency of obtaining mature thyroid cells in vitro remains limited. To enhance the efficiency of in vitro differentiation protocol, we developed a molecular map of the thyroid gland lineage at single-cell resolution. For this, we performed unbiased droplet-based single-cell RNA sequencing of cells from the organoid differentiation protocol. Cluster analysis identified the intermediate stages between stem-cell and mature thyroid. By taking advantage of RNA velocity and pseudo-time trajectory analysis, we identified the key signaling pathways driving thyroid cell differentiation. Specifically, our analysis demonstrated the involvement of TGF-β along with non-canonical Wnt/PCP pathway in regulating thyroid gland lineage. In future, we will pharmacologically manipulate the identified pathways to generate mature and functional thyroid follicular cells in a dish. Overall, our study portrays the power of single-cell gene expression profiling towards improving in vitro organoid models for therapeutic applications. |
