DISSECTING TRANSCRIPTIONAL DEVELOPMENTAL HISTORIES WITH SINGLE-CELL RESOLUTION IN C. ELEGANS

One of the most intriguing questions in developmental biology is how cells acquire their specific cell identities during embryonic development. With the significant development of methods in molecular biology during the last several years and specifically single-cell RNA sequencing, there are more pieces of evidence that development is not necessarily a canalized, linear process. There are more and more pieces of evidence that cells can follow different developmental trajectories to achieve the same terminal identity, through a process that is called convergent differentiation. Nowadays, with the development of single-cell RNA sequencing methods, we have an opportunity to explore changes in cell transcriptomes during development and reveal unconventional ways of lineage specification. In this project, we made an attempt to study the mechanisms that might be responsible for convergent differentiation of a small group of body wall muscle cells in the mesodermal (MS) cell lineage in C. elegans embryos. We obtained single-cell RNA-seq data for ~6500 individual cells, derived from MS cell lineage. We tried to identify potential mechanisms that could be responsible for the activation of the body wall muscle identity in cells that are originally committed to different developmental trajectories. This included experiments with NHR-67 transcription factor, as well as components of the Notch signaling pathway. In addition, we tried to explore the role of pha-4 and hnd-1 transcription factors in the process of establishing commitment of MSxa and MSxp cell lineages during early stages of embryogenesis. Another aspect of the body wall muscle biology that we highlighted in this work is the surprising diversity of terminally differentiated cells in the embryo, diversity that is partially kept at later larval stages. This study serves as a framework for further research projects, providing a good resource for addressing various questions regarding cell identity establishment