Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA.
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA.
Stem Cell Reports. 2023 Jul 11;18(7):1436-1450. doi: 10.1016/j.stemcr.2023.05.016. Epub 2023 Jun 22.
Over the last several years, a method has emerged that endows adult hepatocytes with in vitro proliferative capacity, producing chemically induced liver progenitors (CLiPs). However, there is a growing controversy regarding the origin of these cells. Here, we provide lineage tracing-based evidence that adult hepatocytes acquire proliferative capacity in vitro using rat and mouse models. Unexpectedly, we also found that the CLiP method allows biliary epithelial cells to acquire extensive proliferative capacity. Interestingly, after long-term culture, hepatocyte-derived cells (hepCLiPs) and biliary epithelial cell-derived cells (bilCLiPs) become similar in their gene expression patterns, and they both exhibit differentiation capacity to form hepatocyte-like cells. Finally, we provide evidence that hepCLiPs can repopulate injured mouse livers, reinforcing our earlier argument that CLiPs can be a cell source for liver regenerative medicine. This study advances our understanding of the origin of CLiPs and motivates the application of this technique in liver regenerative medicine.
在过去的几年中，出现了一种使成体肝细胞获得体外增殖能力的方法，从而产生化学诱导的肝祖细胞（CLiP）。然而，关于这些细胞的起源存在越来越多的争议。在这里，我们提供基于谱系追踪的证据，证明使用大鼠和小鼠模型，成体肝细胞在体外获得增殖能力。出乎意料的是，我们还发现 CLiP 方法允许胆管上皮细胞获得广泛的增殖能力。有趣的是，经过长期培养，肝细胞衍生细胞（hepCLiPs）和胆管上皮细胞衍生细胞（bilCLiPs）在基因表达模式上变得相似，并且它们都具有分化能力形成肝细胞样细胞。最后，我们提供了证据表明 hepCLiPs 可以重新填充受伤的小鼠肝脏，这加强了我们之前的观点，即 CLiPs 可以成为肝脏再生医学的细胞来源。这项研究增进了我们对 CLiPs 起源的理解，并促使该技术在肝脏再生医学中的应用。
