Liver progenitor cells perform wound healing in a scratch assay by concerted bistable circuits

Liver progenitor cells (LPC) exhibit the potential to differentiate into both hepatocytes and cholangiocytes, making them promising candidates for cell therapy in cases of severe liver pathology. However, the mechanisms of LPCs regeneration are unclear. Here, we utilised rat liver stem-like epithelial cells (WB-F344) in a wound-healing assay. The scratched near-confluent monolayer (70% area removed) underwent G1-arrest, transient bi-nucleation at 10-12 h post-injury, the epithelial-mesenchymal transition, and motion of cell fraction into the wounded areas. The transient displacement of the nuclear NANOG with upregulated p16^Ink4a, loss of epithelial albumin and CK7 markers, along with transient YAP1/Hippo and TWIST 1 activation, was seen near the wound edge. At 24 h, G1-arrest was overcome, followed by a proliferation boost. At 40-48 h, proliferation was accomplished by reconstitution of epithelial tissue, NANOG was restored in the cell nucleus, and p16^Ink4a left it. Thus, wound healing was performed by concerted, molecular and cellular, bistable circuits.