Beta cell identity changes occur in the islets of donors with diabetes, but the molecular basis of this remains unclear. Protecting residual functional beta cells from cell identity changes may be beneficial for patients with diabetes. A somatostatin-positive cell population was induced in stressed clonal human EndoC-βH1 beta cells and was isolated using FACS. A transcriptomic characterisation of somatostatin-positive cells was then carried out. Gain of somatostatin-positivity was associated with marked dysregulation of the non-coding genome. Very few coding genes were differentially expressed. Potential candidate effector genes were assessed by targeted gene knockdown. Targeted knockdown of the HNRNPD gene induced the emergence of a somatostatin-positive cell population in clonal EndoC-βH1 beta cells comparable with that we have previously reported in stressed cells. We report here a role for the HNRNPD gene in determination of beta cell identity in response to cellular stress. These findings widen our understanding of the role of RNA binding proteins and RNA biology in determining cell identity and may be important for protecting remaining beta cell reserve in diabetes.

中文翻译：

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EndoC-βH1 β 细胞特性的变化可能是由应激诱导的 HNRNPD 消耗介导的

β 细胞身份变化发生在糖尿病供体的胰岛中，但其分子基础仍不清楚。保护残留的功能性 β 细胞免受细胞身份变化的影响可能对糖尿病患者有益。在应激的克隆人 EndoC-βH1 β 细胞中诱导生长抑素阳性细胞群，并使用 FACS 进行分离。然后进行生长抑素阳性细胞的转录组学表征。生长抑素阳性的获得与非编码基因组的显着失调有关。很少有编码基因差异表达。通过靶向基因敲低评估潜在的候选效应基因。HNRNPD 基因的靶向敲低诱导了克隆性 EndoC-βH1 β 细胞中生长抑素阳性细胞群的出现，与我们之前在应激细胞中报道的情况相当。我们在这里报告 HNRNPD 基因在确定响应细胞压力的 β 细胞身份中的作用。这些发现拓宽了我们对 RNA 结合蛋白和 RNA 生物学在确定细胞身份中的作用的理解，并且可能对于保护糖尿病中剩余的 β 细胞储备很重要。