Abstract

BackgroundBone 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.ResultIn 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.ConclusionIn 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.

Highlights

  • Bone marrow mesenchymal stem cells are a potential resource for the clinical therapy of certain diseases

  • In conclusion, to the best of our knowledge, this is the first survey of the transdifferentiation of canine Bone marrow mesenchymal stem cells (BMSCs) into insulin-producing cells according with the timeline using next-generation sequencing technology

  • For the first time induction procedure could be improved based on the transcriptome profiling data At present, existing methods for induction have low efficiency [45], and no consensus has yet been reached regarding the mechanism of transdifferentiation of BMSCs into insulin producing cells

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Summary

Introduction

Bone marrow mesenchymal stem cells are a potential resource for the clinical therapy of certain diseases. 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. Wang et al BMC Genomics (2021) 22:134 clusters, but this is associated with a relatively high risk of neoplasia [8, 9] and other ethical issues [10] Against this background, induced β cells derived from BMSCs are a promising option given that they are easy to obtain and immunoregulation [11, 12], and they can differentiate into osteoblasts, chondrocytes, and adipocytes [13, 14] in vitro. Another option is reprogramming, which can be achieved via the supplementation of small molecules such as conophylline [17]

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