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犬骨髓间充质干细胞向胰岛素产生细胞转分化的转录组分析

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

作者信息

Wang Jinglu, Dai Pengxiu, Zou Tong, Lv Yangou, Zhao Wen, Zhang Xinke, Zhang Yihua

机构信息

The College of Veterinary Medicine of the Northwest Agriculture and Forestry University, No.3 Taicheng Road, Yangling, 712100, Shaanxi, P. R. China.

出版信息

BMC Genomics. 2021 Feb 25;22(1):134. doi: 10.1186/s12864-021-07426-3.

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.

摘要

背景

骨髓间充质干细胞是某些疾病临床治疗的潜在资源。犬作为伴侣动物,与人类生活在同一空间,是人类疾病研究的理想新模型。由于糖尿病患病率高,糖尿病治疗急需替代移植胰岛资源(即胰岛素产生细胞),这使得我们关于骨髓间充质干细胞向胰岛素产生细胞转分化的研究变得更加重要。

结果

在本研究中,我们完成了转分化过程,并对五个样本(两个生物学重复)进行了转录组分析,这五个样本分别是“骨髓间充质干细胞”“胰岛”“阶段1”“阶段2”和“阶段3”,后三个样本是在诱导的第二天、第五天和第八天获得的。在分析数据中总共揭示了11530个差异表达的转录本。差异表达基因的富集分析揭示了几个对调节增殖和转分化至关重要的信号通路,包括粘着斑、细胞外基质-受体相互作用、紧密连接、蛋白质消化和吸收以及Rap1信号通路。同时,获得的蛋白质-蛋白质相互作用网络和功能鉴定表明,三个基因SSTR2、RPS6KA6和VIP的参与可为进一步研究奠定基础。

结论

总之,据我们所知,这是首次使用下一代测序技术按照时间线对犬骨髓间充质干细胞向胰岛素产生细胞的转分化进行的研究。我们挑选出的三个关键基因可能在胰岛素产生细胞转分化过程中调控决定性基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7b/7905582/e74889c45630/12864_2021_7426_Fig1_HTML.jpg

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