Transcriptome Analysis of the Transdifferentiation of canine BMSCs into Insulin Producing Cells

Abstract Background Bone marrow mesenchymal stem cells are a potential resource for the clinical therapy of certain diseases. Canine, as a companion animal, living in the same space with human, is an ideal new model for human diseases research. Because of the high prevalence of diabetes, alternative transplantation islets resource (i.e. insulin producing cells) for diabetes treatment will be in urgent need, which makes our research on the transdifferentiation of Bone marrow mesenchymal stem cells into insulin producing cells become more important.Result In this study, we completed the transdifferentiation process and achieved the transcriptome profiling of five samples with two biological duplicates, namely, “BMSCs”, “islets”, “stage1”, “stage2” and “stage3”, and the latter three samples were achieved on the second, fifth and eighth day of induction. A total of 11,530 differentially expressed transcripts were revealed in the profiling data. The enrichment analysis of differentially expressed genes revealed several signaling pathways that are essential for regulating proliferation and transdifferentiation, including focal adhesion, ECM–receptor interaction, tight junction, protein digestion and absorption, and the Rap1 signaling pathway. Meanwhile, the obtained protein–protein interaction network and functional identification indicating involvement of three genes, SSTR2, RPS6KA6, and VIP could act as a foundation for further research.Conclusion In conclusion, to the best of our knowledge, this is the first survey of the transdifferentiation of canine BMSCs into insulin-producing cells according with the timeline using next-generation sequencing technology. The three key genes we pick out may regulate decisive genes during the development of transdifferentiation of insulin producing cells.

Download Full-text

Transcriptome analysis of the transdifferentiation of canine BMSCs into insulin producing cells

BMC Genomics ◽

10.1186/s12864-021-07426-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jinglu Wang ◽

Pengxiu Dai ◽

Tong Zou ◽

Yangou Lv ◽

Wen Zhao ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Differentially Expressed ◽

Receptor Interaction ◽

Functional Identification ◽

Next Generation Sequencing Technology ◽

Insulin Producing Cells ◽

Junction Protein ◽

Marrow Mesenchymal Stem Cells

Abstract Background Bone marrow mesenchymal stem cells are a potential resource for the clinical therapy of certain diseases. Canine, as a companion animal, living in the same space with human, is an ideal new model for human diseases research. Because of the high prevalence of diabetes, alternative transplantation islets resource (i.e. insulin producing cells) for diabetes treatment will be in urgent need, which makes our research on the transdifferentiation of Bone marrow mesenchymal stem cells into insulin producing cells become more important. Result In this study, we completed the transdifferentiation process and achieved the transcriptome profiling of five samples with two biological duplicates, namely, “BMSCs”, “islets”, “stage 1”, “stage 2” and “stage 3”, and the latter three samples were achieved on the second, fifth and eighth day of induction. A total of 11,530 differentially expressed transcripts were revealed in the profiling data. The enrichment analysis of differentially expressed genes revealed several signaling pathways that are essential for regulating proliferation and transdifferentiation, including focal adhesion, ECM-receptor interaction, tight junction, protein digestion and absorption, and the Rap1 signaling pathway. Meanwhile, the obtained protein–protein interaction network and functional identification indicating involvement of three genes, SSTR2, RPS6KA6, and VIP could act as a foundation for further research. Conclusion In conclusion, to the best of our knowledge, this is the first survey of the transdifferentiation of canine BMSCs into insulin-producing cells according with the timeline using next-generation sequencing technology. The three key genes we pick out may regulate decisive genes during the development of transdifferentiation of insulin producing cells.

Download Full-text

Transcriptome Analysis of the Transdifferentiation of canine BMSCs into Insulin Producing Cells

10.21203/rs.3.rs-32137/v1 ◽

2020 ◽

Author(s):

JINGLU WANG ◽

Pengxiu Dai ◽

Tong Zou ◽

Yangou Lv ◽

Wen Zhao ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Somatostatin Receptor ◽

Differentially Expressed ◽

Receptor Interaction ◽

Functional Identification ◽

Insulin Producing Cells ◽

Junction Protein ◽

Marrow Mesenchymal Stem Cells

Abstract Background Bone marrow mesenchymal stem cells are a potential resource for the clinical therapy of certain diseases. Canine, as a companion animal, living in the same space with human, is an ideal new model for human diseases research. Because of the high prevalence of diabetes, our study in the alternative source of islets from bone marrow mesenchymal stem cells appears to be important.Result In this study, we completed the transdifferentiation process and achieved the transcriptome profiling of five samples with two biological duplicates, namely, “BMSCs”, “islets”, “stage1”, “stage2” and “stage3”. A total of 11,530 differentially expressed transcripts were revealed in the profiling data. The enrichment analysis of differentially expressed genes revealed several signaling pathways that are essential for regulating proliferation and transdifferentiation, including focal adhesion, ECM–receptor interaction, tight junction, protein digestion and absorption, and the Rap1 signaling pathway. Meanwhile, the obtained protein–protein interaction network and functional identification indicating involvement of three genes, somatostatin receptor 2, ribosomal protein S6 kinase A6, and vasoactive intestinal peptide, could act as a foundation for further research.Conclusion In conclusion, to the best of our knowledge, this is the first survey of the transdifferentiation of canine BMSCs into insulin-producing cells according with the timeline using next-generation sequencing technology. The three key genes we pick out may regulate decisive genes during the development of pancreas.

Download Full-text

Combined Transfection of the Three Transcriptional Factors, PDX-1, NeuroD1, and MafA, Causes Differentiation of Bone Marrow Mesenchymal Stem Cells into Insulin-Producing Cells

Experimental Diabetes Research ◽

10.1155/2012/672013 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Guo Qing-Song ◽

Zhu Ming-Yan ◽

Wang Lei ◽

Fan Xiang-Jun ◽

Lu Yu-Hua ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Physiological Function ◽

Insulin Biosynthesis ◽

Insulin Producing Cells ◽

Marrow Mesenchymal Stem Cells ◽

Glucose Challenge ◽

Streptozotocin Induced Diabetes ◽

Treatment Of Diabetes

Aims. The goal of cell transcription for treatment of diabetes is to generate surrogateβ-cells from an appropriate cell line. However, the induced replacement cells have showed less physiological function in producing insulin compared with normalβ-cells.Methods. Here, we report a procedure for induction of insulin-producing cells (IPCs) from bone marrow murine mesenchymal stem cells (BM-mMSCs). These BM-mMSCs have the potential to differentiate into insulin-producing cells when a combination of PDX-1 (pancreatic and duodenal homeobox-1), NeuroD1 (neurogenic differentiation-1), and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homolog A) genes are transfected into them and expressed in these cells.Results. Insulin biosynthesis and secretion were induced in mMSCs into which these three genes have been transfected and expressed. The amount of induced insulin in the mMSCs which have been transfected with the three genes together is significantly higher than in those mMSCs that were only transfected with one or two of these three genes. Transplantation of the transfected cells into mice with streptozotocin-induced diabetes results in insulin expression and the reversal of the glucose challenge.Conclusions. These findings suggest major implications for cell replacement strategies in generation of surrogateβ-cells for the treatment of diabetes.

Download Full-text

Generation of Insulin-Producing Cells from Human Bone Marrow Mesenchymal Stem Cells by Genetic Manipulation

Stem Cells ◽

10.1634/stemcells.2007-0164 ◽

2007 ◽

Vol 25 (11) ◽

pp. 2837-2844 ◽

Cited By ~ 188

Author(s):

Ohad Karnieli ◽

Yael Izhar-Prato ◽

Shlomo Bulvik ◽

Shimon Efrat

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Genetic Manipulation ◽

Human Bone ◽

Human Bone Marrow ◽

Insulin Producing Cells ◽

Marrow Mesenchymal Stem Cells

Download Full-text

Bone marrow mesenchymal stem cells derived from juvenile macaques reversed ovarian ageing in elderly macaques

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02486-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Chuan Tian ◽

Jie He ◽

Yuanyuan An ◽

Zailing Yang ◽

Donghai Yan ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Sex Hormones ◽

Hormone Secretion ◽

The Elderly ◽

Differentially Expressed ◽

Control Group ◽

Functional Changes ◽

Marrow Mesenchymal Stem Cells

Abstract Background Female sex hormone secretion and reproductive ability decrease with ageing. Bone marrow mesenchymal stem cells (BMMSCs) have been postulated to play a key role in treating ovarian ageing. Methods We used macaque ovarian ageing models to observe the structural and functional changes after juvenile BMMSC treatment. Moreover, RNA-seq was used to analyse the ovarian transcriptional expression profile and key pathways through which BMMSCs reverse ovarian ageing. Results In the elderly macaque models, the ovaries were atrophied, the regulation ability of sex hormones was reduced, the ovarian structure was destroyed, and only local atretic follicles were observed, in contrast with young rhesus monkeys. Intravenous infusion of BMMSCs in elderly macaques increased ovarian volume, strengthened the regulation ability of sex hormones, reduced the degree of pulmonary fibrosis, inhibited apoptosis, increased density of blood vessels, and promoted follicular regeneration. In addition, the ovarian expression characteristics of ageing-related genes of the elderly treatment group reverted to that of the young control group, 1258 genes that were differentially expressed, among which 415 genes upregulated with age were downregulated, 843 genes downregulated with age were upregulated after BMMSC treatment, and the top 20 differentially expressed genes (DEGs) in the protein-protein interaction (PPI) network were significantly enriched in oocyte meiosis and progesterone-mediated oocyte maturation pathways. Conclusion The BMMSCs derived from juvenile macaques can reverse ovarian ageing in elderly macaques.

Download Full-text

Dissection of cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells in vivo at single-cell resolution

10.21203/rs.3.rs-1209239/v1 ◽

2022 ◽

Author(s):

Ying Liu ◽

Yan Chen ◽

Xiao-Hua Li ◽

Tian-Peng Li ◽

Chong Cao ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Single Cell ◽

Interaction Analysis ◽

Receptor Interaction ◽

Negative Feedback Regulation ◽

Marrow Mesenchymal Stem Cells

Abstract BackgroundOsteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and play important role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized.ResultsIn this study, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs.ConclusionsAt the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.

Download Full-text