Tbx16 and mesogenin 1 promote presomitic mesoderm differentiation by repressing the mesodermal progenitor cell state

Here, we elucidate how these genes promote differentiation. We use temporally controlled tbx16 and mesogenin 1 overexpression and RNAseq to identify immediate downstream changes in gene expression.

Using machine learning and game theory, we integrated differentially expressed genes with wild-type scRNAseq data and identified genes downstream of tbx16 and mesogenin 1 during mesoderm differentiation. This data-driven analysis indicates that mesogenin 1 and tbx16 primarily repress expression of genes as mesodermal progenitors differentiate. Strikingly, the genes that are most important for defining transcriptional cell states during mesoderm differentiation are most strongly repressed by tbx16 and mesogenin 1.