Immortalization of human preadipocytes
Immortalization of human preadipocytes
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DOI：
10.1016/j.biochi.2003.10.015
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发表时间：
2003-12-01
期刊：
影响因子：
3.9
通讯作者：
Macé, K
中科院分区：
文献类型：
--
作者：
Darimont, C;Macé, K
培养中的原代人前脂肪细胞的特征在于与继代培养期间分化能力的快速下降相关的低增殖能力;从而限制了它们作为细胞模型的用途。细胞永生化是建立具有无限寿命和维持分化能力的细胞系的一种有趣方法。不同的程序开发永生化的人前脂肪细胞进行了讨论。用猿猴病毒40大T抗原（SV 40 T-Ag）转化人前脂肪细胞允许永生化细胞的发育;然而这些细胞不能保持其分化为脂肪细胞的能力。这种限制可能是由于SV 40 T-Ag抑制参与前脂肪细胞分化的转录因子的能力。通过稳定表达人端粒酶催化亚基（hTERT）基因重建端粒酶活性能够部分延长原代前脂肪细胞的寿命，但不能促进细胞永生化。然而，hTERT和人乳头瘤病毒16型E7癌蛋白的联合表达产生了具有无限寿命和保留的成脂潜力的人前脂肪细胞。这种方法似乎是建立人前脂肪细胞系研究脂肪细胞分化和代谢的有效方法。(C)2003年，Elsevier SAS。All rights reserved.
Primary human preadipocytes in culture are characterized by a low proliferative capacity associated with a rapid decline of differentiation ability during subculturing; thereby limiting their use as cellular model. Cellular immortalization constitutes an interesting approach for establishing cell lines presenting an unlimited life span and a maintained differentiation capacity. Different procedures for developing immortalized human preadipocytes are discussed in this review. Transformation of human preadipocytes with the simian virus 40 large T-antigen (SV40 T-Ag) permitted the development of immortalized cells; however these cells could not maintain their capacity to differentiate into adipocytes. This limitation may be explained by the ability of SV40 T-Ag to inhibit transcriptional factors involved in the differentiation of preadipocyte. Reconstitution of the telomerase activity by stable expression of the hTERT (human telomerase catalytic subunit) gene was able to partially extend the lifespan of primary preadipocytes but not to promote cellular immortalization. However, a combined expression of hTERT and the E7 oncoprotein of human papillomavirus type 16, generated human preadipocytes with both an unlimited life span and a preserved adipogenic potential. This approach appears to be an effective method for establishing human preadipose cell lines for studying adipocyte differentiation and metabolism. (C) 2003 Elsevier SAS. All rights reserved.