Cell state transition dynamics at single-cell level

Project Lead: Sui Huang

Co-lead: Lee Hood

Single-cell gene expression and hybrid states. Adherent heterogeneous parental HMLER cells were stained with antibodies against CD24 and CD44 and sorted by flow cytometry followed by single cell qPCR analysis. Every column represents a sorted cell, every row a different gene.

Project 3 extends the need for digitization of biology from molecules to single cells.  In this project, stem cell differentiation to cardiomyocytes will be studied at the single-cell level to identify the discretely distinct cell subpopulations representing the metastable intermediate states in the developmental trajectory to the fully differentiated cardiomyocyte. Sorted (homogeneous) subpopulations afford a novel object for analysis methods that cannot access single cells (e.g., proteomics) and hence offer a new degree of resolution of molecular variables in time courses.  The big question is whether successive discrete quantized cell states mediate cardiomyocyte development —or whether the processes employ amorphous stochastic intermediates.