Integrated mRNA and miRNA profiling revealed deregulation of cellular stress response in bone marrow mesenchymal stem cells derived from patients with immune thrombocytopenia
Integrated mRNA and miRNA profiling revealed deregulation of cellular stress response in bone marrow mesenchymal stem cells derived from patients with immune thrombocytopenia
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整合的 mRNA 和 miRNA 分析揭示了源自免疫性血小板减少症患者的骨髓间充质干细胞的细胞应激反应失调
DOI：
10.1007/s10142-018-0591-2
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发表时间：
2018-05-01
影响因子：
2.9
通讯作者：
Zhang, Xiao-Hui
中科院分区：
文献类型：
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作者：
Zhang, Jia-Min;Zhu, Xiao-Lu;Zhang, Xiao-Hui
由于免疫性血小板减少症（ITP）的复杂性和异质性，我们对该病发病机制的了解仍然有限。最近，我们观察到，骨髓间充质干细胞（MSC）来源于ITP患者表现出的生长缺陷和功能异常，可能参与了自我耐受的崩溃。然而，其潜在机制仍不清楚。在本研究中，我们利用微阵列技术分析了mRNAs和miRNAs的表达，并阐明了ITP患者来源的MSC（MSC-ITP）受损的潜在机制。总之，我们确定了740个基因和32个miRNAs在ITP患者和对照组之间差异表达。未折叠蛋白反应（UPR）受损和DNA转录降低与MSC-ITP显著相关。miRNA与mRNA的相互作用表明，细胞应激反应、UPR和DNA转录可能参与了MSC-ITP中观察到的缺陷。通过RT-PCR进一步验证关键差异表达基因。我们的研究结果强调了细胞应激反应中的缺陷，如受损的UPR和差异DNA转录所示，在导致MSC-ITP中观察到的异常中起关键作用。这些数据可能有助于更好地了解异常骨髓生态位，并提供新的见解ITP的发病机制。
Our understanding of the pathogenesis of immune thrombocytopenia (ITP) remains limited due to the complexity and heterogeneity of the disease. Recently, we observed that bone marrow mesenchymal stem cells (MSCs) derived from ITP patients exhibited growth defects and functional abnormalities that might be involved in the breakdown of self-tolerance. However, the underlying mechanism remains unclear. In this study, we profiled the expression of both mRNAs and miRNAs by utilizing the microarray technique and deciphered the mechanism underlying the impairment of MSCs derived from ITP patients (MSC-ITP). In total, we identified 740 genes and 32 miRNAs that were differentially expressed between ITP patients and controls. A compromised unfolded protein response (UPR) and decreased DNA transcription were shown to be significantly related to MSC-ITP. The interaction of miRNA with mRNA suggested that the cellular stress response, the UPR, and DNA transcription may be involved in the defects observed in MSC-ITP. Key differentially expressed genes were further validated by RT-PCR. Our results highlight that defects in the cellular stress response, as shown by a compromised UPR and differential DNA transcription, play key roles in causing the abnormalities observed in MSC-ITP. These data might contribute to a better understanding of the abnormal bone marrow niche and provide new insights into the pathogenesis of ITP.