Somatic donor cell type correlates with embryonic, but not extra-embryonic, gene expression in postimplantation cloned embryos.
Somatic donor cell type correlates with embryonic, but not extra-embryonic, gene expression in postimplantation cloned embryos.
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DOI：
10.1371/journal.pone.0076422
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ogura A
中科院分区：
文献类型：
--
作者：
Hirasawa R;Matoba S;Inoue K;Ogura A
绝大多数通过体细胞核移植（SCNT）产生的胚胎在植入后显示出确定的异常表型，例如死亡和异常胎盘形成的可能性增加。为了更好地了解潜在的机制，我们分析了从三种不同细胞类型（卵丘细胞，新生儿支持细胞和成纤维细胞）克隆的着床后6.5天小鼠胚胎的全基因组基因表达谱。将从子宫取出的胚胎分离成胚胎（外胚层）和胚外（胚外胚层和外胎盘锥）组织，并进行基因微阵列分析。基因型和性别匹配的胚胎体外受精作为对照。主成分分析显示，尽管胚胎组织中的基因表达模式因供体细胞类型而异，但胚外组织中的基因表达模式在所有组中相对一致。各组胚胎组织中差异表达基因（DEG）均多于胚外组织（P<1.0×10-26）（>2倍于对照组）。在胚胎组织中，常见的异常之一是Dlk 1（一种父系印记基因）的上调。这可能是SCNT产生的小鼠胚胎中偶尔出现仅胎盘的孕体的潜在原因（在我们的实验室中转移的每个胚胎中有1-5%），因为已知相同基因的失调会导致诱导多能干细胞衍生的胚胎发育失败。胚胎外组织中也有一些DEG，这可能解释了SCNT衍生胎盘早期发育不良的原因。这些发现表明，SCNT影响胚胎和胚外发育的差异，并可能导致进一步恶化的胚胎谱系中的供体细胞特异性的方式。这可以解释使用SCNT的克隆效率的供体细胞依赖性变化。
The great majority of embryos generated by somatic cell nuclear transfer (SCNT) display defined abnormal phenotypes after implantation, such as an increased likelihood of death and abnormal placentation. To gain better insight into the underlying mechanisms, we analyzed genome-wide gene expression profiles of day 6.5 postimplantation mouse embryos cloned from three different cell types (cumulus cells, neonatal Sertoli cells and fibroblasts). The embryos retrieved from the uteri were separated into embryonic (epiblast) and extraembryonic (extraembryonic ectoderm and ectoplacental cone) tissues and were subjected to gene microarray analysis. Genotype- and sex-matched embryos produced by in vitro fertilization were used as controls. Principal component analysis revealed that whereas the gene expression patterns in the embryonic tissues varied according to the donor cell type, those in extraembryonic tissues were relatively consistent across all groups. Within each group, the embryonic tissues had more differentially expressed genes (DEGs) (>2-fold vs. controls) than did the extraembryonic tissues (P<1.0×10–26). In the embryonic tissues, one of the common abnormalities was upregulation of Dlk1, a paternally imprinted gene. This might be a potential cause of the occasional placenta-only conceptuses seen in SCNT-generated mouse embryos (1–5% per embryos transferred in our laboratory), because dysregulation of the same gene is known to cause developmental failure of embryos derived from induced pluripotent stem cells. There were also some DEGs in the extraembryonic tissues, which might explain the poor development of SCNT-derived placentas at early stages. These findings suggest that SCNT affects the embryonic and extraembryonic development differentially and might cause further deterioration in the embryonic lineage in a donor cell-specific manner. This could explain donor cell-dependent variations in cloning efficiency using SCNT.
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影响因子：
3.7
作者：
Couldrey C;Wells DN
通讯作者：
Wells DN
影响因子：
3.6
作者：
Inoue, K;Ogonuki, N;Ogura, A
通讯作者：
Ogura, A
影响因子：
30.8
作者：
GUILLEMOT, F;CASPARY, T;NAGY, A
通讯作者：
NAGY, A
影响因子：
4.6
作者：
Donnison, M;Beaton, A;Pfeffer, PL
通讯作者：
Pfeffer, PL
印记 Dlk1-Dio3 区域的激活与小鼠干细胞的多能性水平相关
DOI：
10.1074/jbc.m110.131995
发表时间：
2010-06-18
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Liu L;Luo GZ;Yang W;Zhao X;Zheng Q;Lv Z;Li W;Wu HJ;Wang L;Wang XJ;Zhou Q
通讯作者：
Zhou Q