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摘要 : 胰腺β-细胞具有各种不同的功能,它们在特征上的差异对胰岛素依赖型糖尿病可能会有重要意义。

 胰腺β-细胞具有各种不同的功能,它们在特征上的差异对胰岛素依赖型糖尿病可能会有重要意义。Heiko Lickert及同事发现了一个标记,即Fltp “reporter基因”,该基因表达在成熟的β-细胞中,但在增殖的β-细胞中没有。Fltp的表达是由Wnt信号传导和β-细胞在其组织成三维胰岛时所发生的极化触发的,作者发现,这种架构变化足以诱导小鼠和人类β-细胞成熟。


Identification of proliferative and mature β-cells in the islets of Langerhans


Insulin-dependent diabetes is a complex multifactorial disorder characterized by loss or dysfunction of β-cells. Pancreatic β-cells differ in size, glucose responsiveness, insulin secretion and precursor cell potential1, 2, 3, 4, 5; understanding the mechanisms that underlie this functional heterogeneity might make it possible to develop new regenerative approaches. Here we show that Fltp (also known as Flattop and Cfap126), a Wnt/planar cell polarity (PCP) effector and reporter gene6, acts as a marker gene that subdivides endocrine cells into two subpopulations and distinguishes proliferation-competent from mature β-cells with distinct molecular, physiological and ultrastructural features. Genetic lineage tracing revealed that endocrine subpopulations from Fltp-negative and -positive lineages react differently to physiological and pathological changes. The expression of Fltp increases when endocrine cells cluster together to form polarized and mature 3D islet mini-organs7,8, 9. We show that 3D architecture and Wnt/PCP ligands are sufficient to trigger β-cell maturation. By contrast, the Wnt/PCP effector Fltp is not necessary for β-cell development, proliferation or maturation. We conclude that 3D architecture and Wnt/PCP signalling underlie functional β-cell heterogeneity and induce β-cell maturation. The identification of Fltp as a marker for endocrine subpopulations sheds light on the molecular underpinnings of islet cell heterogeneity and plasticity and might enable targeting of endocrine subpopulations for the regeneration of functional β-cell mass in diabetic patients.

来源: Nature 浏览次数:1


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