Aoyagi Tomomi, Goya Takeshi, Imoto Koji, Azuma Yuki, Hioki Tomonobu, Kohjima Motoyuki, Tanaka Masatake, Oda Yoshinao, Ogawa Yoshihiro
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Gastroenterology, NHO Kyushu Medical Center, Fukuoka, Japan.
Stem Cell Reports. 2025 Jun 10;20(6):102503. doi: 10.1016/j.stemcr.2025.102503. Epub 2025 May 8.
The liver has a robust regenerative capacity. However, the mechanisms underlying this process remain unclear. Numerous studies on liver regeneration have been previously conducted using partial hepatectomy models, which may not fully represent acute liver injury with inflammation and necrosis. This is commonly observed in the majority of clinical cases. In this study, we conducted a single-cell RNA sequencing (RNA-seq) analysis of liver regeneration in acetaminophen-treated mice using publicly available data. We found that two distinct populations of regenerative cells simultaneously appeared within the same regenerative process. The two populations significantly differed in terms of cell morphology, differentiation, localization, proliferation rate, and signal response. Moreover, one of the populations was induced by contact with necrotic tissue and demonstrated a higher proliferative capacity with a dedifferentiated feature. These findings provide new insights into liver regeneration and therapeutic strategies for liver failure.
肝脏具有强大的再生能力。然而，这一过程背后的机制仍不清楚。此前已经使用部分肝切除术模型对肝脏再生进行了大量研究，而该模型可能无法完全代表伴有炎症和坏死的急性肝损伤。这在大多数临床病例中很常见。在本研究中，我们利用公开可用的数据对乙酰氨基酚处理的小鼠肝脏再生进行了单细胞RNA测序（RNA-seq）分析。我们发现，在同一个再生过程中同时出现了两个不同的再生细胞群。这两个细胞群在细胞形态、分化、定位、增殖率和信号反应方面存在显著差异。此外，其中一个细胞群是通过与坏死组织接触诱导产生的，具有更高的增殖能力和去分化特征。这些发现为肝脏再生和肝衰竭的治疗策略提供了新的见解。
