Human Fetal Hepatic Progenitor Cells are Distinct from, but Closely Related to, Hematopoietic Stem/Progenitor Cells
Human Fetal Hepatic Progenitor Cells are Distinct from, but Closely Related to, Hematopoietic Stem/Progenitor Cells
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DOI：
10.1002/stem.1359
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发表时间：
2013-06-01
期刊：
影响因子：
5.2
通讯作者：
Chen, Jianzhu
中科院分区：
文献类型：
--
作者：
Chen, Qingfeng;Khoury, Maroun;Chen, Jianzhu
围绕人肝干细胞和祖细胞的身份和起源有很多争议，部分原因是缺乏小动物模型，其中分离的候选细胞群的发育潜力可以进行功能评估。我们在此表明，从人胎肝过继转移CD 34（+）细胞到亚致死剂量照射的NOD-SCID Il 2 rg（-/-）（NSG）小鼠中，不仅导致了人造血细胞的有效发育，而且还导致了受体小鼠肝脏中人肝细胞样细胞的有效发育。使用这种简单的体内检测结合细胞分级分离，我们发现CD 34（+）胎肝细胞可以分为三个不同的亚群：CD 34（hi）CD 133（hi），CD 34（lo）CD 133（lo）和CD 34（hi）CD 133（neg）。CD 34（hi）CD 133（hi）群体含有造血干/祖细胞（HSPC），因为它们在NSG小鼠中产生T细胞、B细胞、NK细胞、树突状细胞和单核细胞/巨噬细胞，并在体外产生集落形成单位（CFU）-GEMM细胞。CD 34（lo）CD 133（lo）群体不产生造血细胞，但在NSG小鼠和体外可重复产生肝细胞样细胞。CD 34（hi）CD 133（neg）群体在体外仅产生CFU-GM和红系爆发形成单位。此外，我们发现，CD 34（lo）CD 133（lo）细胞表达造血，肝脏和间充质标志物，包括CD 34，CD 133，CD 117，上皮细胞粘附分子，CD 73，白蛋白，α-胎儿蛋白，波形蛋白和转录更密切相关的HSPC比成熟的肝细胞。这些结果表明，CD 34（lo）CD 133（lo）胎肝细胞具有肝祖细胞的特性，人肝祖细胞和造血祖细胞是不同的，虽然它们可能来源于胎肝中相同的前体细胞。
Much controversy surrounds the identity and origin of human hepatic stem and progenitor cells in part because of a lack of small animal models in which the developmental potential of isolated candidate cell populations can be functionally evaluated. We show here that adoptive transfer of CD34(+) cells from human fetal liver into sublethally irradiated NOD-SCID Il2rg(-/-) (NSG) mice leads to an efficient development of not only human hematopoietic cells but also human hepatocyte-like cells in the liver of the recipient mice. Using this simple in vivo assay in combination with cell fractionation, we show that CD34(+) fetal liver cells can be separated into three distinct subpopulations: CD34(hi)CD133(hi), CD34(lo)CD133(lo), and CD34(hi)CD133(neg). The CD34(hi)CD133(hi) population contains hematopoietic stem/progenitor cells (HSPCs) as they give rise to T cells, B cells, NK cells, dendritic cells, and monocytes/macrophages in NSG mice and colony-forming unit (CFU)-GEMM cells in vitro. The CD34(lo)CD133(lo) population does not give rise to hematopoietic cells, but reproducibly generates hepatocyte-like cells in NSG mice and in vitro. The CD34(hi)CD133(neg) population only gives rise to CFU-GM and burst-forming unit-erythroid in vitro. Furthermore, we show that the CD34(lo)CD133(lo) cells express hematopoietic, hepatic, and mesenchymal markers, including CD34, CD133, CD117, epithelial cell adhesion molecule, CD73, albumin, alpha-fetal protein, and vimentin and transcriptionally are more closely related to HSPCs than to mature hepatocytes. These results show that CD34(lo)CD133(lo) fetal liver cells possess the hepatic progenitor cell properties and that human hepatic and hematopoietic progenitor cells are distinct, although they may originate from the same precursors in the fetal liver.