MTHFD1 and cholangiocarcinoma: Compared with the HyPer-high subpopulation CCA cells, CCK8 assays indicated that HyPer-low CCA cells with higher expression levels of MTHFD1 exhibited significant chemoresistance to gemcitabine, whereas MTHFD1 knockdown transformed the gemcitabine chemoresistance of HyPer-low CCA cells into sensitivity, and this transformation could be reversed by NAC treatment (Fig. 4K, L).