Defining Cellular States, Differentiation Trajectories, and Regulatory Networks Through Single Cell Profiling

Transcription factor proteins have long been recognized as key regulators of blood stem cell function. They are thought to act as components of wider regulatory networks, with combinatorial interactions responsible for directing blood stem cell fate choices. However, the complexity of these networks coupled with the infrequency of stem cells have presented formidable challenges for past research efforts aiming to define blood stem cell regulatory networks. Importantly, recent innovations in single cell genomics and computational network inference technologies offer new opportunities to better understand the regulatory network control of blood cell development. The Göttgens group uses a combination of experimental and computational approaches to study how transcription factor networks control the function of blood stem cells and how mutations that perturb such networks cause leukemia. This integrated approach has resulted in the discovery of new combinatorial interactions between key blood stem cell regulators, as well as experimentally validated computational models for blood stem cells. Current research focuses on single cell genomics of early blood development and the development of computer models to chart the transcriptional landscape of blood stem and progenitor cell differentiation.