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The cell biology of cell fate decisions

phluorin imageAlthough most studies of cellular differentiation focus on signaling pathways and transcription factors, many other aspects of cell biology are also important. Our lab is interested in understanding how physical and chemical properties of cells such as pH [1], cytoskeletal dynamics [2], and cell shape [3] contribute to the regulation of cell fate decisions.

Most recently, we have discovered that an increase in intracellular pH occurs spontaneously during differentiation in the follicle stem cell lineage and is required for proper cell fate specification. Our collaborators found that increased intracellular pH is also required for mouse embryonic stem cell differentiation, indicating that changes in intracellular pH promote differentiation in diverse cell types. Little is known about how changes in pH influence cell fate decisions, but changes in pH are known to influence many other processes in the cell, including metabolism, cytoskeletal dynamics, and epigenetics. Thus changes in pH may help to coordinate multiple processes throughout the cell in response to a differentiation cue. We are building on our original observations and conducting forward genetic screens to investigate the role of pH in differentiation. Future studies will also address whether changes in pH are important in other stem cell lineages and whether other changes in the physical and chemical properties of cells also contribute to the regulation of cellular differentiation.