Abstract

The liver has a strong regenerative capacity, but the mechanisms of liver regeneration are not well understood. Furthermore, many previous studies on liver regeneration have been conducted in partial hepatectomy models, which may differ from acute liver injury with inflammation and necrosis, as observed in many clinical cases. In this study, we conducted a single-cell RNA-seq analysis (scRNA-seq) of liver regeneration in mice treated with acetaminophen (APAP) using publicly available data. We discovered that two cell proliferation populations appeared simultaneously during a single regenerative process. The two populations differed significantly in terms of differentiation, localization, proliferation rate, and signal response. Furthermore, one of the populations was induced by contact with necrotic tissue and exhibited a higher proliferative capacity with a dedifferentiated feature. These findings can shed new light on liver regeneration and aid in the development of therapeutic strategies for liver failure.