Tan Zhaoli, Chen Keyan, Shao Yong, Gao Lihua, Wang Yan, Xu Jianming, Jin Yang, Hu Xianwen, Wang Youliang
Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongdajie, Beijing, China.
Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, China.
Dev Growth Differ. 2016 Sep;58(7):620-31. doi: 10.1111/dgd.12307. Epub 2016 Aug 10.
Although liver sinusoidal endothelial cells (LSECs) have long been known to contribute to liver regeneration following injury, the exact role of these cells in liver regeneration remains poorly understood. In this work, we performed lineage tracing of LSECs in mice carrying Tie2-Cre or VE-cadherin-Cre constructs to facilitate fate-mapping of LSECs in liver regeneration. Some YFP-positive LSECs were observed to convert into hepatocytes following a two-thirds partial hepatectomy (PH). Furthermore, human umbilical vein endothelial cells (HUVECs) could be triggered to convert into cells that closely resembled hepatocytes when cultured with serum from mice that underwent an extended PH. These findings suggest that mature non-hepatocyte LSECs play an essential role in mammalian liver regeneration by converting to hepatocytes. The conversion of LSECs to hepatocyte-like (iHep) cells may provide a new approach to tissue engineering.
尽管长期以来人们都知道肝窦内皮细胞（LSECs）在损伤后的肝脏再生中发挥作用，但这些细胞在肝脏再生中的确切作用仍知之甚少。在这项研究中，我们对携带Tie2-Cre或VE-钙黏蛋白-Cre构建体的小鼠的LSECs进行了谱系追踪，以促进LSECs在肝脏再生中的命运图谱绘制。在三分之二部分肝切除术（PH）后，观察到一些YFP阳性的LSECs转化为肝细胞。此外，当用人脐带静脉内皮细胞（HUVECs）与接受延长PH的小鼠血清一起培养时，它们可以被触发转化为与肝细胞非常相似的细胞。这些发现表明，成熟的非肝细胞LSECs通过转化为肝细胞在哺乳动物肝脏再生中发挥重要作用。LSECs向肝细胞样（iHep）细胞的转化可能为组织工程提供一种新方法。
