Neutrophil and macrophage crosstalk might be a potential target for liver regeneration

The regenerative capability of the liver is remarkable, but further research is required to understand the role that neutrophils play in this process. In the present study, we reanalyzed single‐cell RNA sequencing data from a mouse partial hepatectomy (PH) model to track the transcriptional changes in hepatocytes and non‐parenchymal cells. Notably, we unraveled the regenerative capacity of hepatocytes at diverse temporal points after PH, unveiling the contributions of three distinct zones in the liver regeneration process. In addition, we observed that the depletion of neutrophils reduced the survival and liver volume after PH, confirming the important role of neutrophils in liver regeneration. CellChat analysis revealed an intricate crosstalk between neutrophils and macrophages promoting liver regeneration and, using weighted gene correlation network analysis, we identified the most significant genetic module associated with liver regeneration. Our study found that hepatocytes in the periportal zone of the liver are more active than in other zones, suggesting that the crosstalk between neutrophils and macrophages might be a potential target for liver regeneration treatment. Neutrophils interact with macrophages increase the secretion of interleukin (IL)‐6 and hepatocyte growth factor (HGF). This interaction between macrophages and hepatocytes, in turn, promotes liver regeneration. Neutrophils also stimulate the differentiation of monocytes into macrophages, which accelerates liver proliferation. Neutrophil depletion results in a decreased interaction with monocytes and macrophages, which decreases liver regeneration.