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干细胞类型的比较

摘要 : 美国俄勒冈健康与科学大学等处的研究人员比较两种用于重编程成熟细胞为多能干细胞的方法,这项研究首次直接通过比较表明,这两种方法都能够导致细微的分子缺陷。相关文章发表于2014年7月2日的《Nature》杂志上。

新研究将通过“体细胞核转移”(SCNT)方法生成的人类多能干细胞与通过“转录因子介导的重新编程”方法生成的诱导多能干细胞(iPS细胞)的不同遗传特征、表观遗传特征和转录特征进行了比较。这两种细胞类型都是从同一供者体细胞池生成的,以确保基因匹配。iPS细胞和通过SCNT方法生成的胚胎干细胞含有可比的、从头开始的版本数变异。

以前所报告的异常现象(亲本体细胞典型的残留DNA甲基化模式)也如预测的那样在iPS细胞中观察到了,但没有在通过SCNT方法生成的细胞中观察到。这表明,人类体细胞可以通过SCNT方法被忠诚地重新编程为具有多能性,因此与iPS细胞相比也许更适合用于细胞取代治疗。

原文摘要:

Abnormalities in human pluripotent cells due to reprogramming mechanisms

Hong Ma, Robert Morey, Ryan C. O'Neil, Yupeng He, Brittany Daughtry, Matthew D. Schultz, Manoj Hariharan, Joseph R. Nery, Rosa Castanon, Karen Sabatini, Rathi D. Thiagarajan, Masahito Tachibana, Eunju Kang, Rebecca Tippner-Hedges, Riffat Ahmed,Nuria Marti Gutierrez, Crystal Van Dyken, Alim Polat, Atsushi Sugawara, Michelle Sparman,Sumita Gokhale, Paula Amato, Don P.Wolf, Joseph R. Ecker, Louise C. Laurent et al.

Human pluripotent stem cells hold potential for regenerative medicine, but available cell types have significant limitations. Although embryonic stem cells (ES cells) from in vitro fertilized embryos (IVF ES cells) represent the ‘gold standard’, they are allogeneic to patients. Autologous induced pluripotent stem cells (iPS cells) are prone to epigenetic and transcriptional aberrations. To determine whether such abnormalities are intrinsic to somatic cell reprogramming or secondary to the reprogramming method, genetically matched sets of human IVF ES cells, iPS cells and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) were subjected to genome-wide analyses. Both NT ES cells and iPS cells derived from the same somatic cells contained comparable numbers of de novo copy number variations. In contrast, DNA methylation and transcriptome profiles of NT ES cells corresponded closely to those of IVF ES cells, wheras iPS cells differed and retained residual DNA methylation patterns typical of parental somatic cells. Thus, human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal for cell replacement therapies.

对应Nature杂志: 2014年7月10日Nature杂志精选

来源: Nature中文 浏览次数:133

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