Identification of microRNAs expressed highly in pancreatic islet-like cell clusters differentiated from human embryonic stem cells

Authors

  • Bo-Zhi Chen,

    1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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    • Bo-Zhi Chen and Sung-Liang Yu contributed equally to this work.

  • Sung-Liang Yu,

    1. Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei 100, Taiwan
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    • Bo-Zhi Chen and Sung-Liang Yu contributed equally to this work.

  • Sher Singh,

    1. Department of Life Sciences, College of Science, National Taiwan Normal University, Taipei 116, Taiwan
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  • Li-Pin Kao,

    1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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  • Zong-Yun Tsai,

    1. Department of Medicinal and Applied Chemistry, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan
    2. Stem Cell Laboratory, Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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  • Pan-Chyr Yang,

    1. Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 100, Taiwan
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  • Bai-Hsiun Chen,

    1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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  • Steven Shoei-Lung Li

    Corresponding author
    1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
    2. Stem Cell Laboratory, Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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  • The original data of T3pi cells obtained from Affymetrix human genome U133 plus 2.0 GeneChip have been deposited to NCBI database, and the GEO series number is GSE14503.

To whom correspondence should be addressed (email lissl@kmu.edu.tw).

Abstract

Type 1 diabetes is an autoimmune destruction of pancreatic islet beta cell disease, making it important to find a new alternative source of the islet beta cells to replace the damaged cells. hES (human embryonic stem) cells possess unlimited self-renewal and pluripotency and thus have the potential to provide an unlimited supply of different cell types for tissue replacement. The hES-T3 cells with normal female karyotype were first differentiated into EBs (embryoid bodies) and then induced to generate the T3pi (pancreatic islet-like cell clusters derived from T3 cells), which expressed pancreatic islet cell-specific markers of insulin, glucagon and somatostatin. The expression profiles of microRNAs and mRNAs from the T3pi were analysed and compared with those of undifferentiated hES-T3 cells and differentiated EBs. MicroRNAs negatively regulate the expression of protein-coding mRNAs. The T3pi showed very high expression of microRNAs, miR-186, miR-199a and miR-339, which down-regulated the expression of LIN28, PRDM1, CALB1, GCNT2, RBM47, PLEKHH1, RBPMS2 and PAK6. Therefore, these microRNAs and their target genes are very likely to play important regulatory roles in the development of pancreas and/or differentiation of islet cells, and they may be manipulated to increase the proportion of beta cells and insulin synthesis in the differentiated T3pi for cell therapy of type I diabetics.

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