Obesity alters the mouse endometrial transcriptome in a cell context-dependent manner.
Obesity alters the mouse endometrial transcriptome in a cell context-dependent manner.
复制标题
DOI：
10.1186/s12958-022-01030-0
复制
发表时间：
2022-11-24
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
肥胖影响生育能力，与子宫内膜增生和子宫内膜癌的发生呈正相关。子宫内膜上皮常发生疾病驱动突变，而子宫内膜间质对邻近上皮具有高度调控作用。在这里，我们试图确定肥胖小鼠子宫中个体细胞类型中发生的不同转录组变化。将近交系CD-1小鼠饲喂高脂或对照饲料18周，分期发情周期，分离子宫内膜上皮、巨噬细胞和间质进行转录组学分析。高脂肪饮食小鼠表现出体重增加，并出现葡萄糖耐受不良、高胰岛素血症和脂肪肝。肥胖小鼠上皮显示先天免疫和白细胞趋化性相关基因的差异表达。肥胖小鼠基质差异表达与昼夜节律相关的因子，这些基因的表达与葡萄糖耐量或体重相关。我们观察了肥胖小鼠中F4/80 +巨噬细胞数量、Cleaved Caspase 3 （CC3）凋亡标志物染色与葡萄糖耐受不良之间的相关性，包括高CC3 +管腔上皮的肥胖小鼠亚组。该亚群在所有细胞类型中表现出差异的基因表达，在上皮细胞和巨噬细胞中存在与免疫逃逸相关的途径，而在基质中存在与上皮调节相关的失调途径。这些结果表明，上皮细胞和间质细胞的差异反应在肥胖反应中起重要作用，而巨噬细胞在上皮细胞凋亡的背景下失调。子宫微环境细胞中与肥胖相关的基因表达程序可能影响子宫内膜在妊娠期间的功能和影响疾病的发病机制。在线版本包含补充材料，可在10.1186/s12958-022-01030-0获得。
Obesity impacts fertility and is positively correlated with endometrial hyperplasia and endometrial cancer occurrence. Endometrial epithelia often harbor disease driver-mutations, while endometrial stroma are highly regulative of neighboring epithelia. Here, we sought to determine distinct transcriptome changes occurring in individual cell types in the obese mouse uterus. Outbred CD-1 mice were fed high-fat or control diets for 18 weeks, estrous cycle staged, and endometrial epithelia, macrophages, and stroma isolated for transcriptomic analysis. High-fat diet mice displayed increased body mass and developed glucose intolerance, hyperinsulinemia, and fatty liver. Obese mouse epithelia displayed differential gene expression for genes related to innate immunity and leukocyte chemotaxis. The obese mouse stroma differentially expressed factors related to circadian rhythm, and expression of these genes correlated with glucose tolerance or body mass. We observed correlations between F4/80 + macrophage numbers, Cleaved Caspase 3 (CC3) apoptosis marker staining and glucose intolerance among obese mice, including a subgroup of obese mice with high CC3 + luminal epithelia. This subgroup displayed differential gene expression among all cell types, with pathways related to immune escape in epithelia and macrophages, while the stroma dysregulated pathways related to regulation of epithelia. These results suggest an important role for differential response of both the epithelia and stroma in their response to obesity, while macrophages are dysregulated in the context of apoptotic epithelia. The obesity-related gene expression programs in cells within the uterine microenvironment may influence the ability of the endometrium to function during pregnancy and influence disease pathogenesis. The online version contains supplementary material available at 10.1186/s12958-022-01030-0.
登录
查看更多内容
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
6.1
作者：
Bläuer, M;Heinonen, PK;Ylikomi, T
通讯作者：
Ylikomi, T
影响因子：
4.3
作者：
Dukhanina, E. A.;Lukyanova, T. I.;Sashchenko, L. P.
通讯作者：
Sashchenko, L. P.
DOI：
10.1177/2284026518773939
发表时间：
2018-06-01
影响因子：
0.5
作者：
Holdsworth-Carson, Sarah J.;Dior, Uri P.;Girling, Jane E.
通讯作者：
Girling, Jane E.