How are cell fates decided?

  1. At the molecular scale, cellular decisions are instabilities. Cells transition from one defined state into another;

  2. At the cellular scale, cells integrate external cues to trigger or bias molecular fate choices;

  3. At the multicellular scale, cellular signals coordinate homeostasis; and

  4. At tissue or organ scale, homeostatic fixed points adapt over physiological and evolutionary time.

Each of these scales of complexity demands different tools of study, and they invoke conceptually distinct mechanisms. We seek principles by studying them in multiple tissues, and across species.

What tools do we need?

To study cell fate choices, we need to map differentiation hierarchies to determine which decisions are made, and the molecular state of cells that make each decision. We then need tools to track and manipulate cells in different states.

To study how cells coordinate, we need to observe their behaviors through live imaging.

To identify unifying mechanisms across tissues, we would like to simultaneously manipulate and measure changes to cell fate across many tissues. Embryos provide a powerful platform for observing many fate choices at once.

We have introduced droplet microfluidics for single cell genomics, and a range of computational tools to analyze developmental dynamics from single cell RNA-Seq data sets. We also develop statistical approaches to analyze the live cell dynamics, and experimental methods for long-term live imaging. We are passionate about tool development. See our papers and Resources for new methods and tools.