Bykov, Aleksandr et al. (2021) International Worm Meeting "Studying cell-fate convergence in the mesodermal lineage of C. elegans"

Cochella, Luisa, Bykov, Aleksandr, Wang, Jingkui

[International Worm Meeting, 2021]

One of the main goals of developmental biology is to understand the mechanisms and principles of how cells acquire diverse identities during embryogenesis. One of the assumptions is that cells progress through embryogenesis, progressively restricting their developmental potential and gradually acquiring their terminal identities. However, sometimes this process of cell fate specification is not linear. In some cases, cells initially commit towards a specific fate, but later change their seeming commitment and veer towards a different trajectory, converging to another cell type. The C. elegans lineage reveals multiple instances of such cell-type convergence. We aim to understand the mechanisms that initiate the change in a trajectory of a cell, and whether cells with converged identities maintain differences due to their different early transcriptional histories. Using single-cell RNA sequencing and taking advantage of C. elegans's invariant development we have a unique opportunity to study how cells establish their identities at the level of gene regulatory networks with single-cell resolution. We have sequenced the whole mesodermal lineage from C. elegans, originating from the MS blastomere. This lineage gives rise to many body-wall muscles as well as part of the pharynx and contains several instances of cell fate convergence. We used the SMART-Seq2 protocol to achieve maximal sensitivity, which allowed us to detect even lowly expressed transcripts. Using these data, we have uncovered transcriptional differences along trajectories that converge on the production of muscle cells from different parts of the lineage. We are currently testing candidate transcription factors and signaling pathways that may drive this cell identity convergence. We are also exploring the transcriptional differences across terminal muscle cells and their link to the different trajectories. Our data provide new entry points for mechanistic studies to ultimately understand the principles of cell-type diversification.