Single-Cell RNA-Seq Analysis Reveals Lung Epithelial Cell Type-Specific Responses to HDM and Regulation by Tet1.
Single-Cell RNA-Seq Analysis Reveals Lung Epithelial Cell Type-Specific Responses to HDM and Regulation by Tet1.
复制标题
单细胞RNA测序分析揭示了肺上皮细胞对屋尘螨（HDM）的细胞类型特异性反应以及Tet1的调控作用。
作者：
Tet1保护小鼠免受屋尘螨（HDM）诱导的肺部炎症，并改变肺甲基组和转录组。为了探讨Tet1在hdm诱导炎症中个体肺上皮细胞类型中的作用，我们建立了Tet1基因敲除和同胎野生型小鼠hdm诱导的肺炎症模型，然后利用单细胞RNA-seq分析EpCAM+肺上皮细胞。我们鉴定出8种EpCAM+肺上皮细胞类型，其中AT2细胞数量最多。HDM激发改变了上皮细胞类型的相对丰度，并导致细胞类型特异性转录组变化。大量和细胞类型特异性分析还表明，Tet1的缺失导致与hdm诱导的肺部炎症增强相关的基因表达改变，包括警报、解毒酶、氧化应激反应基因和组织修复基因。转录组调节伴随着TF活性的改变。轨迹分析支持HDM可以促进AP和BAS细胞向AT2细胞的分化，而不依赖于Tet1。总的来说，我们的数据表明，肺上皮细胞具有过敏性肺部炎症的共同和独特的转录组特征。Tet1缺失改变了各种肺上皮细胞的转录组网络，这可能促进过敏原诱导的肺部炎症。
Tet1 protects against house dust mite (HDM)-induced lung inflammation in mice and alters the lung methylome and transcriptome. In order to explore the role of Tet1 in individual lung epithelial cell types in HDM-induced inflammation, we established a model of HDM-induced lung inflammation in Tet1 knockout and littermate wild-type mice, then studied EpCAM+ lung epithelial cells using single-cell RNA-seq analysis. We identified eight EpCAM+ lung epithelial cell types, among which AT2 cells were the most abundant. HDM challenge altered the relative abundance of epithelial cell types and resulted in cell type-specific transcriptomic changes. Bulk and cell type-specific analysis also showed that loss of Tet1 led to the altered expression of genes linked to augmented HDM-induced lung inflammation, including alarms, detoxification enzymes, oxidative stress response genes, and tissue repair genes. The transcriptomic regulation was accompanied by alterations in TF activities. Trajectory analysis supports that HDM may enhance the differentiation of AP and BAS cells into AT2 cells, independent of Tet1. Collectively, our data showed that lung epithelial cells had common and unique transcriptomic signatures of allergic lung inflammation. Tet1 deletion altered transcriptomic networks in various lung epithelial cells, which may promote allergen-induced lung inflammation.
登录
查看更多内容
影响因子：
3.9
作者：
Hachim MY;Elemam NM;Ramakrishnan RK;Salameh L;Olivenstein R;Hachim IY;Venkatachalam T;Mahboub B;Al Heialy S;Halwani R;Hamid Q;Hamoudi R
通讯作者：
Hamoudi R
DOI：
10.1155/2021/3524571
发表时间：
2021
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Cui J;Lv Z;Teng F;Yi L;Tang W;Wang W;Tulake W;Qin J;Zhu X;Wei Y;Dong J
通讯作者：
Dong J
影响因子：
7.3
作者：
Baos, Selene;Calzada, David;Cardaba, Blanca
通讯作者：
Cardaba, Blanca
影响因子：
4.6
作者：
Habiel DM;Camelo A;Espindola M;Burwell T;Hanna R;Miranda E;Carruthers A;Bell M;Coelho AL;Liu H;Pilataxi F;Clarke L;Grant E;Lewis A;Moore B;Knight DA;Hogaboam CM;Murray LA
通讯作者：
Murray LA
DOI：
10.4168/aair.2018.10.2.172
发表时间：
2018-03
期刊：
Allergy, asthma & immunology research
影响因子：
--
作者：
Lin TJ;Karmaus WJJ;Chen ML;Hsu JC;Wang IJ
通讯作者：
Wang IJ