Doctoral Researcher University of Helsinki Helsinki, Finland
Abstract: Diabetes mellitus is a chronic condition affecting over 500 million people globally, with profound health and socioeconomic implications. Advances in stem cell-derived islet cell therapies offer hope for restoring glucose regulation but are hindered by the immaturity and heterogeneity of these cells. Current differentiation protocols condense weeks of human pancreatic development into days, bypassing crucial steps in endoderm specification and patterning that are potentially important to properly achieve mature pancreatic cell types. To address this gap, we are establishing 3D gastruloid systems with human pluripotent stem cells that mimic the early stages of human endoderm formation. These models aim to recapitulate the spatial and temporal dynamics of gastrulation, enabling the study of endodermal cell fate decisions and patterning toward pancreatic development. For this purpose, we are utilizing SOX17 and PDX1 reporter stem cell lines that enable agile screening of culture conditions that robustly yield definitive endoderm and pancreatic endoderm, respectively. Using single-cell omics, we are dissecting the genome regulatory mechanisms behind pancreatic endoderm development. By overcoming the current limitations of existing stem cell models based on directed differentiation, self-organizing gastruloid systems advance our understanding of the early stages of human pancreas development, paving the way for improved strategies to treat diabetes using stem cell-derived cellular replacement.
