糖尿病是影响人类健康的重大公共卫生问题，胰岛β细胞功能障碍是发病重要环节之一。诱导多能干细胞（iPSCs）来源的功能性β细胞可为糖尿病提供新的治疗手段，但再生β细胞的成熟性尚待提升。我们前期研究建立的分化策略可显著提高人iPSCs来源β细胞成熟性，并且与转录因子NKX2.2和LncRNA HI-LNC15表达密切相关。已知HI-LNC15参与调控NKX2.2表达，但在体外分化中引入HI-LNC15能否促进人iPSCs成β细胞分化，以及HI-LNC15介导NKX2.2表达的作用机制，尚待研究。我们推测在体外分化过程中引入HI-LNC15可调控NKX2.2表达促进人iPSCs向成熟β细胞分化。本课题拟从分子、细胞、动物水平探讨HI-LNC15提高人iPSCs来源β细胞成熟性的作用及其调控NKX2.2表达的分子机制。本研究将为进一步优化β细胞再生策略提供新思路，为糖尿病干细胞治疗提供有力依据。

Diabetes mellitus is a major public health issue. Pancreatic β-cell dysfunction plays a critical role in the pathogenesis of the disease. Induced pluripotent stem cells (iPSCs)-derived functional β cells provide a new therapeutic option. We have previously developed a novel differentiation strategy that successfully promoted the iPSCs-to-β-cell maturation, which was associated with upregulated expression of the critical transcription factor NKX2.2 and lncRNA HI-LNC15. It has been proven that HI-LNC15 is involved in the modulation of NKX2.2 expression. However, it remains unknown whether the introduction of HI-LNC15 during the in vitro differentiation process would accelerate the iPSCs-to-β-cell maturation. In addition, how does HI-LNC15 exert the above effects remains to be studied. We hypothesize that introducing HI-LNC15 during the in vitro differentiation strategy can upregulate NKX2.2 expression and therefore increase the maturity of iPSCs–derived β cells. This study intends to explore the role of HI-LNC15 in improving the maturation of iPSCs–derived β cells and the underlying mechanism by which HI-LNC15 regulates the expression of NKX2.2, at molecular, cellular and animal levels. Our study will offer new insights for further optimization of β-cell regeneration approach and provide new evidence for diabetes stem cells therapy.