Consequence of Menin Deficiency in Mouse Adipocytes Derived by In Vitro Differentiation.
Consequence of Menin Deficiency in Mouse Adipocytes Derived by In Vitro Differentiation.
复制标题
体外分化衍生的小鼠脂肪细胞中 Menin 缺乏的后果。
DOI：
10.1155/2015/149826
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发表时间：
2015
影响因子：
2.8
通讯作者：
Agarwal,SunitaK
中科院分区：
文献类型：
--
作者：
Parekh,VaishaliI;Modali,SitaD;Desai,ShrutiS;Agarwal,SunitaK
1 型多发性内分泌肿瘤 (MEN1) 综合征患者的脂肪瘤是一种良性脂肪细胞肿瘤，其编码 menin 的 MEN1 双等位基因失活，可作为研究正常和病理性脂肪细胞（脂肪细胞）增殖和功能的模型。 menin 及其靶基因在脂肪细胞中的作用尚不清楚。我们利用体外分化技术，分别从野生型 (WT) 和 menin 缺失 (Men1-KO) 小鼠胚胎干细胞 (mESC) 或未敲除或敲除 menin 的 3T3-L1 细胞中衍生出匹配的正常脂肪细胞和 menin 缺陷脂肪细胞，以研究细胞大小、脂质含量和基因表达变化。来自 Men1-KO mESC 或 3T3-L1 细胞中 menin 敲除后的脂肪细胞显示脂肪细胞大小增加了 1.5-1.7 倍。 mESC 来源的脂肪细胞的整体基因表达分析表明，menin 的缺乏下调了许多差异甲基化基因的表达，包括肿瘤抑制长链非编码 RNA Meg3，但上调了催乳素基因家族基因座的基因表达。我们的结果表明，menin 缺乏会导致脂肪细胞肥大，并提供可用于研究脂肪细胞大小调节的模型系统。
Lipoma in patients with the multiple endocrine neoplasia type 1 (MEN1) syndrome is a type of benign fat‐cell tumor that has biallelic inactivation ofMEN1that encodes menin and could serve as a model to investigate normal and pathologic fat‐cell (adipocyte) proliferation and function. The role of menin and its target genes in adipocytes is not known. We used in vitro differentiation to derive matched normal and menin‐deficient adipocytes from wild type (WT) and menin‐null (Men1‐KO) mouse embryonic stem cells (mESCs), respectively, or 3T3‐L1 cells without or with menin knockdown to investigate cell size, lipid content, and gene expression changes. Adipocytes derived from Men1‐KO mESCs or after menin knockdown in 3T3‐L1 cells showed a 1.5–1.7‐fold increase in fat‐cell size. Global gene expression analysis of mESC‐derived adipocytes showed that lack of menin downregulated the expression of many differentially methylated genes including the tumor suppressor long noncoding RNA Meg3 but upregulated gene expression from the prolactin gene family locus. Our results show that menin deficiency leads to fat‐cell hypertrophy and provide model systems that could be used to study the regulation of fat‐cell size.