lncRNA-mRNA expression profiles and functional networks of mesenchymal stromal cells involved in monocyte regulation

Abstract

Background The goals of this study were to explore the expression profiles and functional networks of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in mesenchymal stromal cells (MSCs) involved in regulating the function of monocytes and to clarify the mechanisms by which MSCs exert immunoregulatory effects on monocytes. Methods MSCs and CD14+ monocytes were separately isolated. The immunoregulatory effects of MSCs on monocytes were determined by flow cytometry. lncRNAs and mRNAs that were differentially expressed (DE) between the control group (MSCs only) and co-culture group (MSCs co-cultured with monocytes) were identified through high-throughput sequencing and bioinformatic analyses and were confirmed by qRT-PCR. Bioinformatic analyses were performed to identify the critical biological functions and signalling pathways involved in MSC-mediated monocyte regulation and to identify the functional networks formed between DE mRNAs and lncRNAs. Results MSCs showed a strong ability to induce monocyte migration but inhibited monocyte differentiation into M1 macrophages. A total of 145 DE lncRNAs and 768 DE mRNAs were identified between the control and co-culture groups. Significant fold changes in lncRNAs and mRNAs were confirmed by qRT-PCR. GO analysis demonstrated that DE mRNAs and lncRNAs were highly associated with terms related to binding and biological regulation. KEGG analysis revealed 122 significantly regulated pathways, including the cytokine-cytokine receptor pathway and chemokine signalling pathway. Interaction and co-expression networks were constructed for DE mRNAs and lncRNAs, and several key microRNAs were identified in the competitive endogenous RNA (ceRNA) network. Target genes of the DE lncRNAs were analysed to predict critical mRNA-lncRNA axes involved in the immunoregulatory function of MSCs. Conclusions Our research describes the lncRNA and mRNA expression profiles and functional networks involved in MSC-mediated regulation of monocytes. These results provide possible molecular mechanisms for the immunoregulatory function of MSCs and may help to elucidate possible molecular therapeutic targets in MSCs for the treatment of autoimmune diseases. Electronic supplementary material The online version of this article (10.1186/s13287-019-1306-x) contains supplementary material, which is available to authorized users.

Effects of long-term culture on the biological characteristics and RNA profiles of human bone-marrow-derived mesenchymal stem cells

“…44 The cross-talk between ceRNAs through shared miRNAs represents a novel layer of gene regulation that plays an important role in the aging of MSCs. 45 However, the specific lncRNAs/circRNAs involved in the immunoreg-ulatory, proliferative, and differentiation capacities of MSCs during aging require further research. Therefore, a core ceRNA network was constructed between DE mRNAs, lncRNAs/circRNAs, and miRNAs based on DE miRNAs targeting interactions, which allowed us to identify several key lncRNAs and circRNAs.…”

LncRNA profile in Hashimoto’s thyroiditis and potential function of NONHSAT079547.2

“…With the development of high-throughput technology, an increasing number of lncRNAs are being detected (Messemaker et al 2018, Li et al 2019a), but only a small number of lncRNAs have been characterized to date. To determine the function of NONHSAT079547.2, we selected the Jurkat cell line to verify the function of cell growth and apoptosis.…”

LncRNA MRF drives the regulatory function on monocyte recruitment and polarization through HNRNPD-MCP1 axis in mesenchymal stem cells

“…Bone marrow was extracted from the posterior superior iliac spine of healthy volunteers under sterile conditions. Then, bone marrow-derived mesenchymal stem cells (BMMSCs) were isolated and purified by density gradient centrifugation as previously reported [ 12 ]. BMMSCs at passage two were used in experiments and cultured in medium composed of 90% Dulbecco’s modified Eagle’s medium (DMEM, Gibco, New York, USA) and 10% fetal bovine serum (FBS, TIANHANG, Zhejiang, China) at 37 °C in a 5% CO 2 atmosphere.…”

“…LncRNA and mRNA high-throughput sequencing was performed as previously described [ 12 ]. Briefly, MSCs (n = 5) cocultured with or without CD14+ monocytes were separately treated with TRIzol (TaKaRa).…”