Differential gene expression profile in monocytic myeloid-derived suppressor cells at maternal-fetal interface in a mouse model of spontaneous abortion
Differential gene expression profile in monocytic myeloid-derived suppressor cells at maternal-fetal interface in a mouse model of spontaneous abortion
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自然流产小鼠模型中母胎界面单核细胞骨髓源性抑制细胞的差异基因表达谱。
DOI：
10.1002/jcp.27902
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发表时间：
2019
影响因子：
5.6
通讯作者：
Lin Yi
中科院分区：
文献类型：
--
作者：
Ren Jiabin;Zeng Weihong;Tian Fuju;Wu Fan;Zhang Siming;Liu Xiaorui;Lin Yi
背景单核细胞髓系衍生抑制细胞(MO-MDSCs)在维持正常妊娠中发挥着重要作用。然而，目前尚不清楚MO-MDSCs的哪些变化可能导致流产，以及当MO-MDSCs作为骨髓源细胞迁移到子宫时，哪些基因表达发生变化。应用Affymetrix 3‘IVT表达谱芯片技术检测自然流产小鼠模型母胎界面MO-MDSCs与正常生育对照组小鼠的差异基因表达谱。结果与正常生育小鼠相比，自然流产小鼠母胎界面MO-MDSCs中3409个基因表达上调，1539个基因表达下调。这些基因在细胞成分、生物学过程、分子功能、蛋白结合、肿瘤信号通路、PI3K-Akt信号通路、瘤内蛋白多糖和细胞外基质受体相互作用等方面都有丰富的表达。此外，我们还发现，与骨髓相比，正常生育小鼠MO-MDSCs中270个基因上调，383个基因在母胎界面下调。这些基因在细胞成分、生物学过程、分子功能、细胞周期、肿瘤转录紊乱和细胞黏附分子等方面均有丰富的表达。结论MO-MDSCs中差异表达的基因可能与母胎免疫耐受妊娠成功有关。
AbstractBackgroundMonocytic myeloid‐derived suppressor cells (MO‐MDSCs) play an important role in maintaining normal pregnancy. However, it is still not clear what kind of changes in MO‐MDSCs may lead to miscarriage, and which gene expression changes take place when MO‐MDSCs migrate to the uterus as bone marrow‐derived cells.MethodsWe used flow sorting technology to obtain MO‐MDSCs from the maternal–fetal interface and bone marrow, respectively. Affymetrix 3′IVT expression profiling chip technology was used to detect the differential gene expression profiles in MO‐MDSCs at the maternal–fetal interface in a mouse model of spontaneous abortion compared with the normal fertility control mice. We also compared the differential gene expression of MO‐MDSCs at the maternal–fetal interface compared with bone marrow in the normal fertility control mice.ResultsWe found that 3,409 genes in MO‐MDSCs were upregulated and 1,539 genes were downregulated at the maternal–fetal interface in the spontaneous abortion mice compared with the normal fertility mice. These genes are enriched in cellular components, biological processes, molecular functions, and protein binding, tumor signaling pathway, the PI3K–Akt signaling pathway, intratumoral proteoglycans, and extracellular matrix receptor interactions. Furthermore, we found that 270 genes in MO‐MDSCs were upregulated and 383 genes were downregulated at the maternal–fetal interface in the normal fertility mice compared with those in the bone marrow. These genes are enriched in cellular components, biological processes, molecular functions, cell cycle, tumor transcriptional disorder, and cell adhesion molecules.ConclusionDifferential gene expression in MO‐MDSCs likely contributes to a successful pregnancy in fetal–maternal immunotolerance.