Fig. 4: Embryonic origin-specific transcription factor binding motif activities and protein interaction profiles.

a Final number and transcription factor (TF) family distribution of non-redundant de novo identified binding motifs across the three embryonic origins. b Differential cluster-specific motif activities in mesenchymal populations across embryonic origins. EC clusters are highlighted in red. c Embryonic origin-specific TF motif activities (left) and mRNA expression profiles (right), enriched in EC cells. d Venn diagram displaying the overlap of chondrocyte-enriched motif activities across embryonic origins. e Motif activity heatmaps of the ten commonly chondrocyte-enriched TF motifs across embryonic origins. The embryonic origin in which the respective motif was identified is indicated by color-coded circles on the right. EC clusters are highlighted in red. f Venn diagram displaying the overlap of unique chondrocyte-enriched motif activities and commonly enriched chondrogenic genes. g Enriched expression of SOX9, SOX5, and FOXP1 in EC cells of the three embryonic origins. Position weight matrices of a TF motif identified in mesenchymal cells of all embryonic origins (SOX9, h) and a TF motif identified in non-mesenchymal cells (skin) of all embryonic origins (TAF1B, i). Pairwise motif similarity scores are displayed on the right, with wider/darker lines indicating higher similarity. j Boxplots of pairwise motif similarity scores for TFs identified in multiple embryonic origins. Motifs were binned according to which general cell population they were identified in, i.e., mesenchymal (n = 204) versus non-mesenchymal (n = 19). Boxplot center line = median, box limits = quartiles, and whiskers = 1.5× inter-quartile range. k Principal component analysis of replicate SOX9 and FOXP1 RIME (Rapid immunoprecipitation mass spectrometry of endogenous proteins) experiments in NC- (N, magenta), somitic mesoderm- (S, blue), and LPM-derived (L, yellow) tissues. Numbers in brackets indicate the percentage of total variance explained by PC1 and PC2. l UpSet plot of significantly differentially abundant (DA) transcription factors and chromatin modifiers identified pairwise across pairs of embryonic origins for SOX9 and FOXP1 RIME experiments. m Averaged log2-normalized intensities for SOX9-specific (left) and FOXP1-specific (right) DA transcription factors and chromatin modifiers across embryonic origins.