Vincent Center of Reproductive Biology/Their 931, Department of Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA.
Endocrinology. 2011 Mar;152(3):1080-9. doi: 10.1210/en.2010-1072. Epub 2011 Jan 5.
The human endometrium is a tissue with remarkable plasticity and regenerative capacity. Additionally, endometrial cells can be retrieved using minimally invasive procedures, which makes them an ideal source for reprogramming into a pluripotent state. Endometrial cells were obtained from donors in their fifth decade and reprogrammed into induced pluripotent stem (iPS) cells using retroviral transduction with SOX2, OCT4, KLF4, and MYC. The human endometrial cells displayed accelerated expression of endogenous NANOG and OCT4 during reprogramming compared with neonatal skin fibroblasts. As a result, iPS cell colonies that could be subcultured and propagated were established as early as 12 d after transduction rather than the usually reported 3-4 wk for other cell types. After 3 wk of reprogramming, the human endometrial cells also yielded significantly higher numbers of iPS colonies in comparison with the neonatal skin fibroblasts. Although the efficiency of iPS colony formation varied depending on the donor, the basal level of endogenous expression of the defined factors was positively correlated with reprogramming efficiency. The reprogramming resulted in an average colony-forming efficiency of 0.49 ± 0.10%, with a range from 0.31-0.66%, compared with the neonatal skin fibroblasts, resulting in an average efficiency of 0.03 ± 0.00% per transduction, with a range from 0.02-0.03%. Our studies show that the human endometrium expresses elevated levels of pluripotent factors, which with additional defined factors, results in significantly more efficient and accelerated generation of induced pluripotent stem cells compared with conventional somatic cells.
人类子宫内膜是一种具有显著可塑性和再生能力的组织。此外，可以通过微创程序获取子宫内膜细胞，这使它们成为重编程为多能状态的理想来源。从 50 岁左右的供体中获取子宫内膜细胞，并使用逆转录病毒转导 SOX2、OCT4、KLF4 和 MYC 将其重编程为诱导多能干细胞（iPS）细胞。与新生儿皮肤成纤维细胞相比，人类子宫内膜细胞在重编程过程中内源 NANOG 和 OCT4 的表达加速。结果，iPS 细胞集落可以在转导后 12 天而不是通常报道的其他细胞类型的 3-4 周进行传代和扩增。重编程 3 周后，与新生儿皮肤成纤维细胞相比，人类子宫内膜细胞产生的 iPS 集落数量也显著增加。尽管 iPS 集落形成的效率取决于供体，但定义因子的内源性表达的基础水平与重编程效率呈正相关。重编程导致平均 iPS 集落形成效率为 0.49±0.10%，范围为 0.31-0.66%，而与新生儿皮肤成纤维细胞相比，平均效率为 0.03±0.00%/转导，范围为 0.02-0.03%。我们的研究表明，人类子宫内膜表达高水平的多能因子，这些因子与其他定义因子一起，导致与传统体细胞相比，iPS 细胞的生成更有效且更快。
