Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver.

Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver.
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DOI:
10.1083/jcb.200108066
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发表时间:
2002-01-07
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Taniguchi H
Taniguchi H
中科院分区:
其他
文献类型:
--
作者:
Suzuki A;Zheng YW;Kaneko S;Onodera M;Fukao K;Nakauchi H;Taniguchi H

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利用流式细胞术和基于单细胞的分析,我们前瞻性地鉴定出具有多系分化潜力和自我更新能力的肝干细胞。这些细胞可以在培养中克隆繁殖,在保持原始干细胞的同时,连续产生肝细胞和胆管细胞作为后代。将体外扩增的细胞移植到受体动物体内,在形态和功能上分化为肝细胞和胆管细胞,肝细胞和胆管结构重构。这些细胞移植到胰腺或十二指肠壁后分化为胰腺导管细胞、腺泡细胞或肠上皮细胞。这些数据表明,自我更新的多能干细胞在发育中的小鼠肝脏中持续存在,并且在适当的微环境下,这些细胞可以被诱导成为其他内胚层起源器官的细胞。肝干细胞的操作可能为消化系统疾病的治疗提供新的见解。
Using flow cytometry and single cell–based assays, we prospectively identified hepatic stem cells with multilineage differentiation potential and self-renewing capability. These cells could be clonally propagated in culture where they continuously produced hepatocytes and cholangiocytes as descendants while maintaining primitive stem cells. When cells that expanded in vitro were transplanted into recipient animals, they morphologically and functionally differentiated into hepatocytes and cholangiocytes with reconstitution of hepatocyte and bile duct structures. Furthermore, these cells differentiated into pancreatic ductal and acinar cells or intestinal epithelial cells when transplanted into pancreas or duodenal wall. These data indicate that self-renewing pluripotent stem cells persist in the developing mouse liver and that such cells can be induced to become cells of other organs of endodermal origin under appropriate microenvironment. Manipulation of hepatic stem cells may provide new insight into therapies for diseases of the digestive system.
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