Single cell decision making in development and dedifferentiation

Our goal is to understand how cells make stochastic cell fate decisions in development and dedifferentiation. Understanding how individual cells make decisions has until recently been intractable, because gene expression has been measured from population averages. These averages mask the dynamics and differences between cells that define development or dedifferentiation in complex cell populations. Recently, we have pioneered approaches to visualize the transcription of individual genes in single, living cells. This means we can continually monitor the expression of cell fate regulators in single cells as they commit to fate decisions. We will now combine our imaging methods with molecular genetics, to test the hypothesis that stochastic cell fate choices in development are derived from heterogeneity in the expression of cell fate regulators. To determine how cells overcome the rate-limiting steps in dedifferentiation, we will use our technologies to dissect the gene expression dynamics required for successful reversal of the differentiated state. Overall our work will define the fundamental characteristics of the gene expression underlying stochastic fate choices in development, and provide new directions for developing safe, effective regenerative medicine.