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非人灵长类动物中基于卵母细胞和基于因子的核重编程的全转录组分析。

Global transcriptional analysis of oocyte-based and factor-based nuclear reprogramming in the nonhuman primate.

作者信息

Byrne James

机构信息

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095, USA.

出版信息

Cell Reprogram. 2011 Dec;13(6):473-81. doi: 10.1089/cell.2011.0033. Epub 2011 Sep 15.

Abstract

The mechanisms of nuclear reprogramming following somatic cell nuclear transfer (SCNT) to enucleated oocytes or factor-based reprogramming are poorly understood. In this study global transcriptional analysis was performed on a number of different rhesus monkey (Macaca mulatta) cell and tissue samples, including rhesus-induced pluripotent stem cells (IPSCs) and rhesus SCNT-derived embryonic stem cells (SCNT-ESCs). Global transcriptional cluster analysis and stem cell-specific gene expression analysis both suggested that the oocyte-reprogrammed SCNT-ESCs were transcriptionally closer to the control fertilized ESCs than IPSCs. These results, combined with previous epigenetic analysis studies in the mouse, reinforce the hypothesis that oocyte-reprogrammed cell nuclei are more completely reprogrammed to an ESC state than IPSCs. Transcriptional analysis of rhesus oocytes detected over 500 ESC-specific genes, including OCT3/4, NR5A2, and DNMT3B. These results, combined with previously published reprogramming research, were used as the basis for a general model to explain the mechanisms of nuclear reprogramming.

摘要

体细胞经核移植(SCNT)到去核卵母细胞或基于因子的重编程后的核重编程机制尚不清楚。在本研究中,对许多不同的恒河猴(猕猴)细胞和组织样本进行了全转录组分析,包括恒河猴诱导多能干细胞(iPSC)和恒河猴SCNT来源的胚胎干细胞(SCNT-ESC)。全转录组聚类分析和干细胞特异性基因表达分析均表明,经卵母细胞重编程的SCNT-ESC在转录水平上比iPSC更接近对照受精ESC。这些结果与之前在小鼠中的表观遗传学分析研究相结合,强化了这样一种假设,即经卵母细胞重编程的细胞核比iPSC更完全地重编程为ESC状态。对恒河猴卵母细胞的转录组分析检测到500多个ESC特异性基因,包括OCT3/4、NR5A2和DNMT3B。这些结果与之前发表的重编程研究相结合,被用作解释核重编程机制的通用模型的基础。

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