Two types of regeneration mechanism in acute liver injury

Tomomi Aoyagi, Takeshi Goya, Koji Imoto, Yuki Azuma, Tomonobu Hioki, Motoyuki Kohjima, Masatake Tanaka, Yoshinao Oda, Yoshihiro Ogawa
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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.
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急性肝损伤的两种再生机制
肝脏具有很强的再生能力,但人们对肝脏再生的机制还不甚了解。此外,以往许多有关肝脏再生的研究都是在肝部分切除模型中进行的,这可能与许多临床病例中观察到的伴有炎症和坏死的急性肝损伤不同。在本研究中,我们利用公开数据对对乙酰氨基酚(APAP)治疗小鼠的肝脏再生进行了单细胞RNA-seq分析(scRNA-seq)。我们发现,在一个再生过程中同时出现了两个细胞增殖群。这两种细胞群在分化、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而诱发的,并表现出较高的增殖能力和去分化特征。这些发现可为肝脏再生带来新的启示,并有助于肝衰竭治疗策略的开发。
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