Paternal uniparental disomy 14 and related disorders: placental gene expression analyses and histological examinations.
Paternal uniparental disomy 14 and related disorders: placental gene expression analyses and histological examinations.
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DOI：
10.4161/epi.21937
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发表时间：
2012-10
期刊：
影响因子：
3.7
通讯作者：
Ogata T
中科院分区：
文献类型：
--
作者：
Kagami M;Matsuoka K;Nagai T;Yamanaka M;Kurosawa K;Suzumori N;Sekita Y;Miyado M;Matsubara K;Fuke T;Kato F;Fukami M;Ogata T
虽然最近对父系单亲14[UPD(14)PAT]患者和其他影响染色体14q32.2印迹区域的疾病的研究已经成功地确定了与UPD(14)PAT表型发生有关的潜在表观遗传学因素，但仍有几个问题有待阐明，包括RTL1表达的调控机制(S)、dio3的印迹状态和胎盘组织学特征。因此，我们使用来自两名UPD(14)PAT患者的新鲜胎盘样本进行了分子研究。我们观察到RTL1在两个患者的胎盘样本中的表达水平大约是对照胎盘样本的5倍，而Dio3在两个患者的胎盘样本中的表达水平与对照胎盘样本中的表达水平相似。接下来，我们使用上述新鲜胎盘样本和福尔马林固定和石蜡包埋的胎盘样本进行了组织学研究，这些样本来自一名母亲来源的微缺失患者，涉及DLK1、-IG-DMR、MEG3-DMR和MEG3。末梢绒毛可见血管内皮细胞肿胀，周细胞肥大，毛细血管管腔狭窄。DLK1、RTL1和Dio3蛋白在血管内皮细胞和周细胞中特异表达，且蛋白染色程度与相应基因的表达剂量密切相关。这些结果表明，RTL1as编码的microRNA可以抑制RTL1的表达，并反对dio3是父系表达的基因。此外，推测DLK1、DIO3，特别是RTL1蛋白在血管内皮细胞和周细胞的发育中起着关键作用。
Although recent studies in patients with paternal uniparental disomy 14 [upd(14)pat] and other conditions affecting the chromosome 14q32.2 imprinted region have successfully identified underlying epigenetic factors involved in the development of upd(14)pat phenotype, several matters, including regulatory mechanism(s) for RTL1 expression, imprinting status of DIO3 and placental histological characteristics, remain to be elucidated. We therefore performed molecular studies using fresh placental samples from two patients with upd(14)pat. We observed that RTL1 expression level was about five times higher in the placental samples of the two patients than in control placental samples, whereas DIO3 expression level was similar between the placental samples of the two patients and the control placental samples. We next performed histological studies using the above fresh placental samples and formalin-fixed and paraffin-embedded placental samples obtained from a patient with a maternally derived microdeletion involving DLK1, the-IG-DMR, the MEG3-DMR and MEG3. Terminal villi were associated with swollen vascular endothelial cells and hypertrophic pericytes, together with narrowed capillary lumens. DLK1, RTL1 and DIO3 proteins were specifically identified in vascular endothelial cells and pericytes, and the degree of protein staining was well correlated with the expression dosage of corresponding genes. These results suggest that RTL1as-encoded microRNA functions as a repressor of RTL1 expression, and argue against DIO3 being a paternally expressed gene. Furthermore, it is inferred that DLK1, DIO3 and, specially, RTL1 proteins, play a pivotal role in the development of vascular endothelial cells and pericytes.
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DOI：
10.1038/ejhg.2012.26
发表时间：
2012-09
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
通讯作者：
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影响因子：
--
作者：
Fowden, AL;Sibley, C;Constancial, M
通讯作者：
Constancial, M
影响因子：
30.8
作者：
Kagami, Masayo;Sekita, Yoichi;Ogata, Tsutomu
通讯作者：
Ogata, Tsutomu
影响因子：
9.2
作者：
Davis, E;Caiment, F;Charlier, C
通讯作者：
Charlier, C
影响因子：
30.8
作者：
Sekita, Yoichi;Wagatsuma, Hirotaka;Ishino, Fumitoshi
通讯作者：
Ishino, Fumitoshi