PMID- 38273351 OWN - NLM STAT- MEDLINE DCOM- 20240129 LR - 20240206 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 15 IP - 1 DP - 2024 Jan 25 TI - Dysregulated lncRNAs regulate human umbilical cord mesenchymal stem cell differentiation into insulin-producing cells by forming a regulatory network with mRNAs. PG - 22 LID - 10.1186/s13287-023-03572-5 [doi] LID - 22 AB - OBJECTIVE: In recent years, cell therapy has emerged as a new research direction in the treatment of diabetes. However, the underlying molecular mechanisms of mesenchymal stem cell (MSC) differentiation necessary to form such treatment have not been clarified. METHODS: In this study, human umbilical cord mesenchymal stem cells (HUC-MSCs) isolated from newborns were progressively induced into insulin-producing cells (IPCs) using small molecules. HUC-MSC (S0) and four induced stage (S1-S4) samples were prepared. We then performed transcriptome sequencing experiments to obtain the dynamic expression profiles of both mRNAs and long noncoding RNAs (lncRNAs). RESULTS: We found that the number of differentially expressed lncRNAs and mRNAs trended downwards during differentiation. Gene Ontology (GO) analysis showed that the target genes of differentially expressed lncRNAs were associated with translation, cell adhesion, and cell connection. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the NF-KB signalling pathway, MAPK signalling pathway, HIPPO signalling pathway, PI3K-Akt signalling pathway, and p53 signalling pathway were enriched in these differentially expressed lncRNA-targeting genes. We also found that the coexpression of the lncRNA CTBP1-AS2 with PROX1 and the lncRNAs AC009014.3 and GS1-72M22.1 with JARID2 mRNA was related to the development of pancreatic beta cells. Moreover, the coexpression of the lncRNAs: XLOC_ 050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14- AS1, RP11-148K1.12, and CTD2020K17.3 with p53, regulated insulin secretion by pancreatic beta cells. CONCLUSION: In this study, HUC-MSCs combined with small molecule compounds were successfully induced into IPCs. Differentially expressed lncRNAs may regulate the insulin secretion of pancreatic beta cells by regulating multiple signalling pathways. The lncRNAs AC009014.3, Gs1-72m21.1, and CTBP1-AS2 may be involved in the development of pancreatic beta cells, and the lncRNAs: XLOC_050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14-AS1, RP11-148K1.12, and CTD2020K17.3 may be involved in regulating the insulin secretion of pancreatic beta cells, thus providing a lncRNA catalogue for future research regarding the mechanism of the transdifferentiation of HUC-MSCs into IPCs. It also provides a new theoretical basis for the transplantation of insulin-producing cells into diabetic patients in the future. CI - (c) 2024. The Author(s). FAU - Xie, Tianqin AU - Xie T AD - Department of Endocrinology Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China. FAU - Huang, Qiming AU - Huang Q AD - The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translation Medicine, Nanchang University, Nanchang of Jiangxi, China. FAU - Huang, Qiulan AU - Huang Q AD - Department of Endocrinology Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China. FAU - Huang, Yanting AU - Huang Y AD - Department of Endocrinology Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China. FAU - Liu, Shuang AU - Liu S AD - Department of Endocrinology Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China. FAU - Zeng, Haixia AU - Zeng H AD - Department of Endocrinology Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China. FAU - Liu, Jianping AU - Liu J AD - Department of Endocrinology Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China. liujpnfm@163.com. LA - eng GR - 2500 dollars/the National Natural Science Foundation of China (no. 81760150 and 82160162)/ GR - 2500 dollars/the Science and Technology Program of Jiangxi Province (20165BCB18019 and 20202ACBL206008)/ GR - 2000 dollars/the Key Program (No.20192ACB70004), the Key Research Project (No.20192BBH80015) and the Project for Leading Talent (No.20204BCJ22035) of Department of Science and Technology, Jiangxi Province/ PT - Journal Article DEP - 20240125 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Messenger) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (Insulins) SB - IM MH - Humans MH - Infant, Newborn MH - *RNA, Long Noncoding/genetics/metabolism MH - RNA, Messenger/genetics/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Tumor Suppressor Protein p53/genetics MH - *Mesenchymal Stem Cells/metabolism MH - Umbilical Cord/metabolism MH - *Insulins/genetics/metabolism MH - Gene Regulatory Networks MH - Gene Expression Profiling PMC - PMC10809572 OTO - NOTNLM OT - Diabetes mellitus OT - Insulin-producing cells OT - Long noncoding RNA OT - Small molecule OT - Umbilical cord mesenchymal stem cells COIS- Funding bodies are QMH and JPL, QMH participated in the experiments. JPL participated in the study design and provided critical revision. The authors declare that there is no conflict of interest. The authors declare that there is no conflict of interest. EDAT- 2024/01/26 00:43 MHDA- 2024/01/29 06:42 PMCR- 2024/01/25 CRDT- 2024/01/25 23:40 PHST- 2021/11/18 00:00 [received] PHST- 2023/11/16 00:00 [accepted] PHST- 2024/01/29 06:42 [medline] PHST- 2024/01/26 00:43 [pubmed] PHST- 2024/01/25 23:40 [entrez] PHST- 2024/01/25 00:00 [pmc-release] AID - 10.1186/s13287-023-03572-5 [pii] AID - 3572 [pii] AID - 10.1186/s13287-023-03572-5 [doi] PST - epublish SO - Stem Cell Res Ther. 2024 Jan 25;15(1):22. doi: 10.1186/s13287-023-03572-5.