Diabetes is a pandemic manifested through glucose dysregulation mediated by inadequate insulin secretion by beta cells. A beta cell replacement strategy would transform the treatment paradigm from pharmacologic glucose modulation to a genuine cure. Stem cells have emerged as a potential source for beta cell (β-cell) engineering. The detailed generation of functional β-cells from both embryonic and induced pluripotent stem cells has recently been described. Adult stem cells, including adipose derived, may also offer a therapeutic approach, but remain ill defined. In our study, we performed an in-depth assessment of insulin-producing beta cells generated from human adipose, irrespective of donor patient age, gender, and health status. Cellular transformation was confirmed using flow cytometry and single-cell imaging. Insulin secretion was observed with glucose stimulation and abrogated following palmitate exposure, a common free fatty acid implicated in human beta cell dysfunction. We used next-generation sequencing to explore gene expression changes before and after differentiation of patient-matched samples, which revealed more than 5,000 genes enriched. Adipose-derived beta cells displayed comparable gene expression to native β-cells. Pathway analysis demonstrated relevance to stem cell differentiation and pancreatic developmental processes, which are vital to cellular function, structural development, and regulation. We conclude that the functions associated with adipose derived beta cells are mediated through relevant changes in the transcriptome, which resemble those seen in native β-cell morphogenesis and maturation. Therefore, they may represent a viable option for the clinical translation of stem cell-based therapies in diabetes.

中文翻译：

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探索人类脂肪干细胞衍生 β 细胞的基因组景观

糖尿病是一种大流行病，表现为由β细胞胰岛素分泌不足介导的葡萄糖失调。β细胞替代策略将把治疗范式从药物葡萄糖调节转变为真正的治愈。干细胞已成为β细胞（β细胞）工程的潜在来源。最近已经描述了从胚胎和诱导多能干细胞中详细生成功能性 β 细胞。成体干细胞，包括源自脂肪的干细胞，也可能提供一种治疗方法，但仍不明确。在我们的研究中，我们对人类脂肪产生的产生胰岛素的 β 细胞进行了深入评估，无论供体患者的年龄、性别和健康状况如何。使用流式细胞术和单细胞成像确认细胞转化。在葡萄糖刺激下观察到胰岛素分泌，并在棕榈酸酯暴露后消失，棕榈酸酯是一种与人类 β 细胞功能障碍有关的常见游离脂肪酸。我们使用下一代测序来探索患者匹配样本分化前后的基因表达变化，结果显示超过 5,000 个基因富集。脂肪来源的 β 细胞显示出与天然 β 细胞相当的基因表达。通路分析表明与干细胞分化和胰腺发育过程相关，这对细胞功能、结构发育和调节至关重要。我们得出结论，与脂肪衍生的 β 细胞相关的功能是通过转录组的相关变化介导的，这类似于天然 β 细胞形态发生和成熟中所见的变化。所以，