Here, we show that HTR2B+/high cells have a higher NOTCH activity compared to HTR2B−/low CRC cells, NOTCH3+/high CRC organoid cells have an enhanced EMT phenotype and a higher HTR2B level, and we also detected the overlap between HTR2B + and NOTCH3 + cells in tumors, suggesting the common features of these two cell populations. The gene discussed is NOTCH3; the disease is colorectal carcinoma.