Linking regulatory networks to transcriptional identity at the single cell level

During developmental differentiation cells confront numerous cell fate decisions. These decisions are determined, or at least influenced by the integration of external signals with internal state through gene regulatory networks. The output of this process is an increasingly complex set of transcriptional identities that can be considered as a phase space occupancy. Research on bulk populations of cells has been very successful at identifying important components of the regulatory processes; however, relatively little is known about the quantitative relationships between components and this means that the resulting networks have little or no predictive power. Such information has been difficult to obtain as measurements need to be performed at the single cell level. We have been tackling this problem by developing in situ based methods for quantifying transcriptional identity within single cells through the direct counting of gene transcripts. This has allowed us to consider how transcriptional identity changes during differentiation of lateral mesoderm and we have combined this with inducible transcription factor expression to start to quantify the underlying regulation. In future work I wish to combine quantification of the transmission of external signals with the transcriptional response in order to dissect the mechanisms that drive cell fate decisions.