A conserved bacterial protein induces pancreatic beta cell expansion during zebrafish development
A conserved bacterial protein induces pancreatic beta cell expansion during zebrafish development
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DOI：
10.7554/elife.20145
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发表时间：
2016-12-13
期刊：
影响因子：
7.7
通讯作者：
Guillemin, Karen
中科院分区：
文献类型：
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作者：
Hill, Jennifer Hampton;Franzosa, Eric A.;Guillemin, Karen
常驻微生物在胃肠道的发育中起着重要作用，但它们对其他消化器官的影响还没有得到很好的研究。使用gnotobiotic斑马鱼，我们发现在早期幼虫发育期间胰腺β细胞群的正常扩增需要肠道微生物群，并且特定的细菌成员可以恢复正常的β细胞数量。这些细菌共享编码先前未描述的蛋白质的基因，该蛋白质在本文中被命名为BefA（β细胞扩增因子A），其足以在发育中的斑马鱼幼虫中诱导β细胞增殖。BefA的同源物存在于几种人类相关的细菌物种中，我们表明它们具有保守的刺激斑马鱼幼鱼β细胞增殖的能力。我们的研究结果强调了微生物群在早期胰腺β细胞发育中的作用，并为低多样性儿童粪便微生物群与糖尿病风险增加之间的关联提供了可能的基础。
Resident microbes play important roles in the development of the gastrointestinal tract, but their influence on other digestive organs is less well explored. Using the gnotobiotic zebrafish, we discovered that the normal expansion of the pancreatic beta cell population during early larval development requires the intestinal microbiota and that specific bacterial members can restore normal beta cell numbers. These bacteria share a gene that encodes a previously undescribed protein, named herein BefA (beta Cell Expansion Factor A), which is sufficient to induce beta cell proliferation in developing zebrafish larvae. Homologs of BefA are present in several human associated bacterial species, and we show that they have conserved capacity to stimulate beta cell proliferation in larval zebrafish. Our findings highlight a role for the microbiota in early pancreatic beta cell development and suggest a possible basis for the association between low diversity childhood fecal microbiota and increased diabetes risk.