Characterization of the COPD alveolar niche using single-cell RNA sequencing.
Characterization of the COPD alveolar niche using single-cell RNA sequencing.
复制标题
使用单细胞RNA测序表征COPD肺泡生态位。
DOI：
10.1038/s41467-022-28062-9
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发表时间：
2022-01-25
影响因子：
16.6
通讯作者：
Rosas IO
中科院分区：
文献类型：
--
作者：
Sauler M;McDonough JE;Adams TS;Kothapalli N;Barnthaler T;Werder RB;Schupp JC;Nouws J;Robertson MJ;Coarfa C;Yang T;Chioccioli M;Omote N;Cosme C Jr;Poli S;Ayaub EA;Chu SG;Jensen KH;Gomez JL;Britto CJ;Raredon MSB;Niklason LE;Wilson AA;Timshel PN;Kaminski N;Rosas IO
慢性阻塞性肺疾病(COPD)是世界范围内主要的死亡原因，然而，我们对COPD病理生物学基础上的细胞特异性机制的了解仍然不完全。在这里，我们分析了来自晚期COPD患者或对照肺的移植肺组织的单细胞RNA测序图谱，并使用暴露于香烟烟雾10个月的小鼠肺的单细胞RNA测序、分离的人类肺泡上皮细胞的RNA测序、体外功能模型以及人肺组织样本的原位杂交和免疫染色来验证研究结果。我们确定了肺泡上皮II型细胞亚群，其转录证据表明COPD患者细胞代谢异常和细胞应激耐力降低。利用转录网络分析，我们预测在COPD中毛细血管内皮细胞会被炎症，特别是通过增加CXCL基序趋化因子信号。最后，我们检测到一个高金属硫蛋白表达的巨噬细胞亚群在晚期COPD中丰富。总而言之，这些发现突出了晚期COPD病理生物学中涉及的特定细胞机制。慢性阻塞性肺疾病是世界范围内主要的死亡原因，而我们对其病理生物学基础上的细胞特异性机制的了解仍不完全。在这里，作者对人类肺组织进行scRNA-seq，以确定与疾病相关的肺泡龛细胞的转录变化。
Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide, however our understanding of cell specific mechanisms underlying COPD pathobiology remains incomplete. Here, we analyze single-cell RNA sequencing profiles of explanted lung tissue from subjects with advanced COPD or control lungs, and we validate findings using single-cell RNA sequencing of lungs from mice exposed to 10 months of cigarette smoke, RNA sequencing of isolated human alveolar epithelial cells, functional in vitro models, and in situ hybridization and immunostaining of human lung tissue samples. We identify a subpopulation of alveolar epithelial type II cells with transcriptional evidence for aberrant cellular metabolism and reduced cellular stress tolerance in COPD. Using transcriptomic network analyses, we predict capillary endothelial cells are inflamed in COPD, particularly through increased CXCL-motif chemokine signaling. Finally, we detect a high-metallothionein expressing macrophage subpopulation enriched in advanced COPD. Collectively, these findings highlight cell-specific mechanisms involved in the pathobiology of advanced COPD. Chronic obstructive pulmonary disease is a leading cause of death worldwide, while our understanding of cell-specific mechanisms underlying its pathobiology remains incomplete. Here the authors perform scRNA-seq of human lung tissue to identify transcriptional changes in alveolar niche cells associated with the disease.
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影响因子：
82.9
作者：
Cloonan SM;Glass K;Laucho-Contreras ME;Bhashyam AR;Cervo M;Pabón MA;Konrad C;Polverino F;Siempos II;Perez E;Mizumura K;Ghosh MC;Parameswaran H;Williams NC;Rooney KT;Chen ZH;Goldklang MP;Yuan GC;Moore SC;Demeo DL;Rouault TA;D'Armiento JM;Schon EA;Manfredi G;Quackenbush J;Mahmood A;Silverman EK;Owen CA;Choi AM
通讯作者：
Choi AM
影响因子：
64.8
作者：
Gillich A;Zhang F;Farmer CG;Travaglini KJ;Tan SY;Gu M;Zhou B;Feinstein JA;Krasnow MA;Metzger RJ
通讯作者：
Metzger RJ
金属转运蛋白 Slc39a10 通过控制巨噬细胞存活来调节对炎症刺激的敏感性
DOI：
10.1073/pnas.1708018114
发表时间：
2017-12-05
影响因子：
11.1
作者：
Gao H;Zhao L;Wang H;Xie E;Wang X;Wu Q;Yu Y;He X;Ji H;Rink L;Min J;Wang F
通讯作者：
Wang F
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P