Microbial regulation of the L cell transcriptome.
Microbial regulation of the L cell transcriptome.
复制标题
L细胞转录组的微生物调节。
DOI：
10.1038/s41598-017-18079-2
复制
发表时间：
2018-01-19
影响因子：
4.6
通讯作者：
Bäckhed F
中科院分区：
文献类型：
--
作者：
Arora T;Akrami R;Pais R;Bergqvist L;Johansson BR;Schwartz TW;Reimann F;Gribble FM;Bäckhed F
L细胞是一类重要的肠内分泌细胞，分泌具有多种代谢和生理作用的激素，如胰高血糖素样肽-1和肽YY。肠道是影响宿主生理学的数万亿细菌的家园，但对微生物群如何影响L细胞中的基因表达的理解有限。因此，我们将报告小鼠品系GLU-Venus重新衍生为无菌（GF），该小鼠品系在胰高血糖素原基因的控制下表达黄色荧光蛋白。分离来自GF和常规饲养（CONV-R）GLU-Venus小鼠的回肠和结肠的Lpos细胞，并进行转录组学分析。我们观察到微生物群对回肠L细胞产生主要影响。基因本体富集分析显示，微生物群抑制与来自回肠的Lpos细胞中的囊泡定位和突触囊泡循环相关的生物过程。通过Lpos细胞的电子显微镜检查证实了这一发现，显示囊泡数量减少，并且与GF GLU-Venus小鼠相比，CONV-R小鼠回肠原代培养物中细胞内GLP-1含量降低。通过分析GF小鼠定殖后的Lpos细胞，我们观察到在定殖的1天内最大的转录调节是明显的。因此，微生物群对主要在回肠中的L细胞转录组具有快速和显著的影响。
L cells are an important class of enteroendocrine cells secreting hormones such as glucagon like peptide-1 and peptide YY that have several metabolic and physiological effects. The gut is home to trillions of bacteria affecting host physiology, but there has been limited understanding about how the microbiota affects gene expression in L cells. Thus, we rederived the reporter mouse strain, GLU-Venus expressing yellow fluorescent protein under the control of the proglucagon gene, as germ-free (GF). Lpos cells from ileum and colon of GF and conventionally raised (CONV-R) GLU-Venus mice were isolated and subjected to transcriptomic profiling. We observed that the microbiota exerted major effects on ileal L cells. Gene Ontology enrichment analysis revealed that microbiota suppressed biological processes related to vesicle localization and synaptic vesicle cycling in Lpos cells from ileum. This finding was corroborated by electron microscopy of Lpos cells showing reduced numbers of vesicles as well as by demonstrating decreased intracellular GLP-1 content in primary cultures from ileum of CONV-R compared with GF GLU-Venus mice. By analysing Lpos cells following colonization of GF mice we observed that the greatest transcriptional regulation was evident within 1 day of colonization. Thus, the microbiota has a rapid and pronounced effect on the L cell transcriptome, predominantly in the ileum.
登录
查看更多内容
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
29
作者：
Donohoe DR;Garge N;Zhang X;Sun W;O'Connell TM;Bunger MK;Bultman SJ
通讯作者：
Bultman SJ
影响因子：
29
作者：
Reimann F;Habib AM;Tolhurst G;Parker HE;Rogers GJ;Gribble FM
通讯作者：
Gribble FM
胆汁酸主要通过进入基底外侧G蛋白偶联的胆汁酸受体触发GLP-1。
影响因子：
4.8
作者：
Brighton CA;Rievaj J;Kuhre RE;Glass LL;Schoonjans K;Holst JJ;Gribble FM;Reimann F
通讯作者：
Reimann F
影响因子：
7.7
作者：
Tolhurst G;Heffron H;Lam YS;Parker HE;Habib AM;Diakogiannaki E;Cameron J;Grosse J;Reimann F;Gribble FM
通讯作者：
Gribble FM