Ductal cells have been proposed as a source of adult β cell neogenesis, but this has remained controversial. By combining lineage tracing, 3D imaging, and single-cell RNA sequencing (scRNA-seq) approaches, we show that ductal cells contribute to the β cell population over time. Lineage tracing using the Neurogenin3 (Ngn3)-CreERT line identified ductal cells expressing the endocrine master transcription factor Ngn3 that were positive for the δ cell marker somatostatin and occasionally co-expressed insulin. The number of hormone-expressing ductal cells was increased in Akita^+/− diabetic mice, and ngn3 heterozygosity accelerated diabetes onset. scRNA-seq of Ngn3 lineage-traced islet cells indicated that duct-derived somatostatin-expressing cells, some of which retained expression of ductal markers, gave rise to β cells. This study identified Ngn3-expressing ductal cells as a source of adult β cell neogenesis in homeostasis and diabetes, suggesting that this mechanism, in addition to β cell proliferation, maintains the adult islet β cell population.

导管细胞已被提议作为成人 β 细胞新生的来源，但这仍然存在争议。通过结合谱系追踪、3D 成像和单细胞 RNA 测序 (scRNA-seq) 方法，我们表明随着时间的推移，导管细胞对 β 细胞群有贡献。使用 Neurogenin3 (Ngn3)-CreERT 系进行谱系追踪，鉴定出表达内分泌主转录因子 Ngn3 的导管细胞，这些细胞对 δ 细胞标记物生长抑素呈阳性，偶尔还共表达胰岛素。Akita ^+/-糖尿病小鼠中表达激素的导管细胞数量增加，而ngn3杂合子加速了糖尿病的发作。Ngn3 谱系追踪胰岛细胞的 scRNA-seq 表明导管来源的生长抑素表达细胞（其中一些保留了导管标记物的表达）产生了 β 细胞。这项研究确定了表达 Ngn3 的导管细胞是体内平衡和糖尿病中成人 β 细胞新生的来源，表明除了 β 细胞增殖之外，这种机制还可以维持成人胰岛 β 细胞群。