Programming Gene Expression in hiPSC-derived Organoids

Engineering transgenes to drive cell type-specific expression

We apply our genome engineering technologies to human iPSCs to tackle research questions spanning basic and translational research.

Firstly, we apply our synthetic genomics workflow to investigate gene regulatory mechanisms and program gene expression in hiPSC-derived cells and organoids. Specifically, we study a genomic locus encoding two master developmental transcription factors, CDX2 and PDX1. The genes show mutually exclusive expression in some cell types, while their expression overlaps in others. 

We generate various 100kb synthetic transgenes that re-write the PDX1-CDX2 regulatory domain and integrate these at a safe harbour locus. To model the in vivo expression domains of PDX1/CDX2, we differentiate genome-engineered hiPSCs into relevant cell types and organoids. With this we not only aim to decipher the regulatory logic encoding their distinct expression patterns but also learn how to program such cell-type specific expression patterns for clinically relevant next-generation transgenes. 

Secondly, we develop advanced transgene integration strategies and screen transgene integration sites in hiPSCs. Here, our aim is to identify new candidate loci for integration of therapeutically relevant transgenes.

Involved Team Members

Hannah Wieler

Nele Kagelmacher

Julia Schwedek