Abstract
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.
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- ITP:
-
immune thrombocytopenia
- MSCs:
-
mesenchymal stem cells
- UPR:
-
unfolded protein response
- ER:
-
endoplasmic reticulum
- GSEA:
-
gene set enrichment analysis
- GO:
- DCs:
-
dendritic cells
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Funding
This work was supported by National Natural Science Foundation of China (No. 81470343 and No. 81670116), Beijing Natural Science Foundation (No. 7171013), Beijing Municipal Science and Technology Commission (No. Z171100001017084), and The National Key Research and Development Progran of China (No. 2017YFA0105503).
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Jia-Min Zhang and Xiao-Hui Zhang conceived and designed the study; Xiao-Lu Zhu and Jing Xue performed the experiments; Ying-Jun Chang analyzed the data; Jia-Min Zhang wrote the paper; X. Long Zheng, Kai-Yan Liu, and Xiao-Jun Huang oversaw the work and critically revised the manuscript; Xiao-Hui Zhang attracted funding.
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All the patients and controls provided consent to participate in the study, which was approved by the Ethics Committee of the Peking University People’s Hospital and conducted in accordance with the Declaration of Helsinki.
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The authors declare that they have no conflict of interest.
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Zhang, JM., Zhu, XL., Xue, J. et al. Integrated mRNA and miRNA profiling revealed deregulation of cellular stress response in bone marrow mesenchymal stem cells derived from patients with immune thrombocytopenia. Funct Integr Genomics 18, 287–299 (2018). https://doi.org/10.1007/s10142-018-0591-2
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DOI: https://doi.org/10.1007/s10142-018-0591-2