Keynote Talk: Decoding Cellular Signals: Commitment during Hes Cells Differentiation

During cell decision-making signal transduction networks dynamically change in
time and space in response to cues, and thereby trigger different cellular states.
The SMAD protein networks are conserved signaling modules that regulate cell
fate decisions by transducing a myriad of growth factor signals. How information
is decoded and transmitted through SMAD networks in order to commit to a
specific cell fate is a fundamental, yet unanswered, question.
Human embryonic stem cells (hESC) are an ideal system for addressing this
question as they have the propensity to differentiate into any of the three germ
layers. Bone morphogenetic protein 4 (BMP4) triggers hES cells differentiation
towards mesoderm, via SMAD signaling. Here, we investigated how BMP4 signals
are first decoded by SMAD signaling networks and found that in single hES cells,
commitment to mesoderm differentiation is an unexpectedly early event. By
combining quantitative imaging of SMAD activation dynamics in hES cells,
RNAseq and mathematical modelling we show how BMP4 signals are first
encoded by SMAD signaling networks and how SMAD dynamics is decoded
intracellularly to irreversibly commit to hES differentiation.