BACKGROUND We have previously shown that SLE BMSC have decreased proliferation, increased ROS, increased DNA damage and repair (DDR), a senescence associated secretory phenotype, and increased senescence-associated β-galactosidase. We have also shown SLE BMSC produce increased amounts of interferon beta (IFNβ), have increased mRNA for several genes induced by IFNβ, and have a pro-inflammatory feedback loop mediated by a MAVS. To better understand the phenotype of SLE BMSC we conducted mRNA sequencing. METHODS Patients fulfilling SLE classification criteria and age and sex matched healthy controls were recruited under an Institutional Review Board approved protocol. Bone marrow aspirates and peripheral blood samples were obtained. BMSC were isolated and grown in tissue culture. Early passage BMSC were harvested and mRNA samples were sent for RNAseq. Serum samples were assayed for IFNβ by ELISA. RESULTS On the basis of top differentially expressed genes between SLE and healthy controls, SLE patients with high levels of serum IFNβ clustered together while SLE patients with low levels of IFNβ clustered with healthy controls. Those genes differentially expressed in SLE patients generally belonged to known IFN pathways, and showed a strong overlap with the set of genes differentially expressed in IFNβ high subjects, per se. Moreover, gene expression changes induced by treating healthy BMSC with exogenous IFNβ were remarkably similar to gene expression differences in SLE IFNβ high vs low BMSC. CONCLUSIONS BMSCs from SLE patients are heterogeneous. A subgroup of SLE BMSC is distinguished from other SLE BMSC and from controls by increased levels of mRNAs induced by type I interferons. This subgroup of SLE patients had increased levels of IFNβ in vivo.

中文翻译：

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来自 SLE 患者的骨髓间充质干细胞在体外培养过程中保持干扰素特征

背景我们之前已经表明，SLE BMSC 增殖减少、ROS 增加、DNA 损伤和修复 (DDR) 增加、衰老相关的分泌表型和衰老相关的 β-半乳糖苷酶增加。我们还显示 SLE BMSC 产生更多的干扰素 β (IFNβ)，增加了由 IFNβ 诱导的几种基因的 mRNA，并具有由 MAVS 介导的促炎反馈回路。为了更好地了解 SLE BMSC 的表型，我们进行了 mRNA 测序。方法 根据机构审查委员会批准的方案招募符合 SLE 分类标准和年龄和性别匹配的健康对照的患者。获得骨髓抽吸物和外周血样品。BMSC 被分离并在组织培养中生长。收获早期传代 BMSC，并将 mRNA 样品送至 RNAseq。通过ELISA测定血清样品的IFNβ。结果在SLE与健康对照差异表达基因最高的基础上，血清IFNβ水平高的SLE患者聚集在一起，而IFNβ水平低的SLE患者与健康对照聚集。在 SLE 患者中差异表达的那些基因通常属于已知的 IFN 途径，并且与在 IFNβ 高的受试者中差异表达的一组基因本身显示出强烈的重叠。此外，用外源性 IFNβ 处理健康 BMSC 诱导的基因表达变化与 SLE IFNβ 高与低 BMSC 的基因表达差异非常相似。结论 SLE 患者的 BMSCs 是异质的。SLE BMSC 的一个亚组与其他 SLE BMSC 和对照组的区别在于 I 型干扰素诱导的 mRNA 水平增加。