Grant: Project Grant

Cells continuously sense their external and internal environments to both adapt and perform specific functions. They process such information through intracellular networks of proteins, which are often organized into specific structures or circuits, to induce specific responses. One such biological response involves conversion one cell fate (or type) to another. Conversion of cell fate is fundamental to development of an organism - progenitor cells such as pluripotent cells go through series of cell fate decisions to give rise to variety of adult cell types, and is often misrelated in disease. The differences among individual genetically identical cells response to a condition often also generates both molecular as well as cellular heterogeneity allowing them to exhibit diverse cell states. For instance, pluripotent stem cells exhibit such heterogeneous cell states: Totipotent, Pluripotent and differentiation-Primed, each with distinct differentiation capacity. Pluripotent stem cells are increasingly used for disease modelling and regenerative medicine. By introducing multiple sources of differentiation bias, such multiple cell states compromise the effective use of pluripotent cells. Thus, it is highly important to understand the molecular basis of pluripotent stem cell states. What are their potential cell states? What are the key regulatory mechanisms governing their transitions? Can we control and reverse-engineer such mechanisms to modulate the cell states? We propose to address these in the current grant. We will study the cell states of pluripotent stem cells at the single-cell level using our expertise in the interdisciplinary systems biology approach - combining quantitative single-cell experiments in proteomics and genomics with computational biology.