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将人子宫内膜成纤维细胞重编程为诱导多能干细胞。

Reprogramming human endometrial fibroblast into induced pluripotent stem cells.

机构信息

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.

出版信息

Taiwan J Obstet Gynecol. 2012 Mar;51(1):35-42. doi: 10.1016/j.tjog.2012.01.008.

DOI:10.1016/j.tjog.2012.01.008
PMID:22482966
Abstract

OBJECTIVE

A recent breakthrough demonstrated that ectopic expression of four genes is sufficient to reprogram human fibroblasts into inducible pluripotent stem cells (iPSCs). However, it remains unknown whether human endometrial fibroblasts (EMFs) are capable of being reprogrammed into EMF-derived iPSCs (EMF-iPSCs).

METHODS

EMFs were obtained from donors in their third and fourth decade of life and were reprogrammed into iPSCs using retroviral transduction with Oct-4, Sox2, Klf4, and c-Myc.

RESULTS

The EMF-iPSCs displayed the accelerated expression of endogenous Nanog and OCT-4 during reprogramming compared with EMFs. As a result, EMF-iPSC colonies that could be subcultured and propagated were established as early as 12 days after transduction. After 2 weeks of reprogramming, the human endometrial cells yielded significantly higher numbers of iPSC colonies and formed more 3D spheroid bodies than the EMFs. We have shown that human EMF-iPSCs are able to differentiate into neuronal-like cells, adipocytes, and osteocyte-like cells that express specific osteogenic genes.

CONCLUSION

Human EMFs can undergo reprogramming to establish pluripotent stem cell lines in female donors by the retroviral transduction of Oct-4, Sox2, Klf4, and c-Myc.

摘要

目的

最近的一项突破表明,异位表达四个基因足以将人成纤维细胞重编程为诱导多能干细胞(iPSCs)。然而,目前尚不清楚人子宫内膜成纤维细胞(EMFs)是否能够被重编程为源自 EMF 的 iPSCs(EMF-iPSCs)。

方法

从处于第三和第四十年龄段的供体中获得 EMFs,并使用 Oct-4、Sox2、Klf4 和 c-Myc 的逆转录病毒转导将其重编程为 iPSCs。

结果

与 EMFs 相比,EMF-iPSCs 在重编程过程中显示出内源性 Nanog 和 OCT-4 的表达加速。结果,在转导后 12 天就可以建立可传代和增殖的 EMF-iPSC 集落。经过 2 周的重编程,与 EMFs 相比,人子宫内膜细胞产生的 iPSC 集落数量明显更多,并形成更多的 3D 球体。我们已经表明,人 EMF-iPSCs 能够分化为神经元样细胞、脂肪细胞和成骨细胞样细胞,这些细胞表达特定的成骨基因。

结论

通过 Oct-4、Sox2、Klf4 和 c-Myc 的逆转录病毒转导,人 EMFs 可以在女性供体中进行重编程,建立多能干细胞系。

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