Integrated mRNA and miRNA profiling revealed deregulation of cellular stress response in bone marrow mesenchymal stem cells derived from patients with immune thrombocytopenia

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.