利用示踪新技术研究成体胰腺β细胞增殖异质性

糖尿病作为一种以高血糖为主要病征的代谢性疾病已经成为严重威胁人类健康的一大杀手。胰腺β细胞分泌胰岛素参与血糖稳态维持，探索如何促进β细胞增殖是领域内亟待解决的重点和难点问题。已有不同研究组报道促进β细胞增殖的方法，然而对于β细胞增殖的检测主要基于免疫染色和和核苷酸类似物掺入，分辨率较低且无法做到长时程准确记录β细胞增殖情况，所以目前领域内缺乏可以原位检测β细胞增殖的有效技术手段。我们聚焦这一前沿科学问题，基于双同源重组遗传谱系示踪系统，建立了一种可以长时程不间断记录体内β细胞增殖的新型遗传技术，将阐明不同生理病理状态下β细胞增殖情况，回答β细胞增殖异质性还是均一性这个重要科学问题，并探索内在调控机制，筛选与优化有效促进β细胞增殖的方法。该项目可以为准确检测体内β细胞增殖提供强大的技术支撑，为糖尿病临床治疗研究提供重要理论信息和新的研究方向，具有重要科学意义和潜在应用前景。

As the most common metabolic disease worldwide, diabetes threatens human’s health and lives severely. Insulin secreted by pancreatic β-cells has an important role in the maintenance of blood glucose homeostasis. Exploring effective pathways to enhance β-cell proliferation is an important yet unsolved task in the field. Different groups have reported several methods to promote β-cell proliferation. However, the detection of in vivo β-cell proliferation is mainly based on the immunostaining and the incorporation of nucleotide analogs, the resolution of which are low and long-term recording of β-cell proliferation cannot be achieved. Thus, there is a lack of effective technical methods that can detect β-cell proliferation in vivo at present. To resolve this cutting-edge scientific issue, we have established a new genetic technology that can record the proliferation of β-cells in vivo for a long time at a significantly higher resolution based by using dual homologous recombination genetic lineage tracing system. In this work, we will use this system to clarify the proliferation of β-cells under various physiological and pathological conditions and address the important scientific question on whether β-cell proliferation is heterogeneity or uniformity. We will also explore the mechanism, screen and optimize methods to promote β-cell proliferation. This work can provide powerful technical support for the accurate detection of β-cell proliferation in vivo, and the research results can provide important theoretical information and new therapeutic targets for the clinical treatment of diabetes.