Every cell in the human body descents from a single fertilized oocyte (egg) which consist of 50% each of the genetic information of both parents. However, the human body consists of hundreds of different cell types with very diverse functions despite all cells having the same genetic information (collectively named the genome). Different cell types cells arise as the fertilized oocyte divides to form the embryo. Cell-type diversification occurs through the activation of different regions of the genome in different cells. This process is directed by epigenetics, which involves the more or less tight packaging of the DNA in proteins collectively termed chromatin. Yet, how exactly cells take cell-fate decisions, and what the underlying epigenetic mechanism are, is poorly understood especially in early embryonic development. Thus to obtain better insight in this process, it is essential to develop techniques with which the identity of a cell can be determined in conjunction with the epigenetic regulatory state of that same single cell. For Q4 of our project, we finalized a new single-cell technique to measure epigenetic and transcriptomic states in individual cells. We implemented this technique to study gene regulation and genome organization in mouse and zebrafish embryogenesis. We obtained new insight into how transcription factor networks are controlled by chromatin states during cellular specification in mouse cells and uncovered potentially new roles for densely packed chromatin in providing mechanical stiffness to the notochord in zebrafish 15-somite stage. By implementing this technique, our group will continue to collect information on the contribution of epigenetics in directing cell choice in embryonic development in different organisms. The method and the publicly available computational pipeline will facilitate research of other research groups to study diverse biological questions.
