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首页> 外文期刊>Development >GDF11 modulates NGN3+ islet progenitor cell number and promotes {beta}-cell differentiation in pancreas development.
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GDF11 modulates NGN3+ islet progenitor cell number and promotes {beta}-cell differentiation in pancreas development.

机译：GDF11调节NGN3 +胰岛祖细胞数量，并促进胰腺发育中的{beta}细胞分化。

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摘要

Identification of endogenous signals that regulate expansion and maturation of organ-specific progenitor cells is a major goal in studies of organ development. Here we provide evidence that growth differentiation factor 11 (GDF11), a member of the TGF-beta ligand family, governs the number and maturation of islet progenitor cells in mouse pancreas development. Gdf11 is expressed in embryonic pancreatic epithelium during formation of islet progenitor cells that express neurogenin 3. Mice deficient for Gdf11 harbor increased numbers of NGN3(+) cells, revealing that GDF11 negatively regulates production of islet progenitor cells. Despite a marked expansion of these NGN3(+) islet progenitors, mice lacking Gdf11 have reduced beta-cell numbers and evidence of arrested beta-cell development, indicating that GDF11 is also required for beta-cell maturation. Similar precursor and islet cell phenotypes are observed in mice deficient for SMAD2, an intracellular signaling factor activated by TGF-beta signals. Our data suggest that Gdf11 and Smad2 regulate islet cell differentiation in parallel to the Notch pathway, which previously has been shown to control development of NGN3(+) cells. Thus, our studies reveal mechanisms by which GDF11 regulates the production and maturation of islet progenitor cells in pancreas development.
机译：鉴定调节器官特异性祖细胞的扩增和成熟的内源性信号是器官发育研究的主要目标。在这里，我们提供证据表明，生长分化因子11（GDF11）是TGF-β配体家族的成员，它决定着小鼠胰腺发育中胰岛祖细胞的数量和成熟度。 Gdf11在表达神经生成素3的胰岛祖细胞形成过程中在胚胎胰腺上皮中表达。缺乏Gdf11的小鼠具有数量增多的NGN3（+）细胞，这表明GDF11对胰岛祖细胞的产生负调节作用。尽管这些NGN3（+）胰岛祖细胞显着扩展，但缺少Gdf11的小鼠的β细胞数量减少，并且β细胞发育停止的证据表明，GDF11对于β细胞成熟也是必需的。在缺乏SMAD2的小鼠中观察到相似的前体和胰岛细胞表型，SMAD2是一种由TGF-β信号激活的细胞内信号转导因子。我们的数据表明，Gdf11和Smad2平行于Notch通路调节胰岛细胞分化，以前已证明它可以控制NGN3（+）细胞的发育。因此，我们的研究揭示了GDF11调节胰腺发育中胰岛祖细胞产生和成熟的机制。

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