Furthermore, they both identified BEST4-ECs and GCs as two endpoints of the trajectory, further supporting the view of multidirectional differentiation trajectories of epithelial cells during CRC progression and revealing the complexity and plasticity of epithelial cell fate determination during tumour development (40, 41) (Figure 4J, K, Supplementary Figures S4D–F). This evidence concerns the gene BEST4 and colorectal carcinoma.