Endogenous PROM1 activation redistributes liver cancer cells along a preexisting differentiation axis

In PLC/PRF/5 hepatocellular carcinoma cells, sustained CRISPR activation of endogenous PROM1 shifts cells away from a hepatocyte-like, PROM1-low compartment toward intermediate states along a preexisting differentiation axis.

• Why it matters: CD133 is used as a stem-like marker in HCC, but its functional role in regulating tumor-cell state and differentiation programs is not well defined.
• What they did: The authors defined a PROM1-responsive transcriptional axis using acute CRISPR activation and PROM1 knockdown, then used single-cell profiling to map how endogenous PROM1 heterogeneity aligns with compartmentalization.
• The result: The hepatocyte-like compartment decreases and cells redistribute along the axis after sustained PROM1 activation, with related patterns observed in an independent HuH-7 dataset and a human HCC case.

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