Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury.
Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury.
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COVID-19肺炎的空间转录组表征鉴定出与组织损伤有关的免疫回路。
DOI：
10.1172/jci.insight.157837
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发表时间：
2023-01-24
期刊：
影响因子：
8
通讯作者：
Issa, Fadi
中科院分区：
文献类型：
--
作者：
Cross, Amy R.;Andrea, Carlos E. de;Villalba-Esparza, Maria;Landecho, Manuel F.;Cerundolo, Lucia;Weeratunga, Praveen;Etherington, Rachel E.;Denney, Laura;Ogg, Graham;Ho, Ling -Pei;Roberts, Ian S. D.;Hester, Joanna;Klenerman, Paul;Melero, Ignacio;Sansom, Stephen N.;Issa, Fadi
新冠肺炎造成的严重肺损伤涉及不同群体的免疫细胞和基质细胞之间的复杂相互作用。在这项研究中，我们使用空间转录组学方法来描绘新冠肺炎感染肺组织中存在的细胞、途径和基因，这些细胞、通路和基因存在于组织病理损伤的整个光谱中。我们应用基于相关网络的方法去卷积来自46个感兴趣区域的基因表达数据，覆盖来自3名患者保存完好的肺样本中的超过62,000个细胞。尽管患者间有很大的异质性，但我们发现在严重组织中存在共同的免疫细胞信号通路的证据，该通路涉及细胞毒性淋巴细胞和促炎巨噬细胞之间的串扰。细胞毒性淋巴细胞表达IFNG与CXCL9、CXCL10和CXCL11等趋化因子的诱导有关，CXCL9、CXCL10和CXCL11被认为促进CXCR3+免疫细胞的募集。肿瘤坏死因子超家族成员BAFF(TNFSF13B)和TRAIL(TNFSF10)在组织损伤严重的区域持续上调。我们使用已发表的空间和单细胞SARS-CoV-2数据集来验证我们在其他新冠肺炎患者队列中的肺组织中的发现。由此产生的严重新冠肺炎免疫介导的组织病理模型可能为未来的治疗策略提供参考。
Severe lung damage resulting from COVID-19 involves complex interactions between diverse populations of immune and stromal cells. In this study, we used a spatial transcriptomics approach to delineate the cells, pathways, and genes present across the spectrum of histopathological damage in COVID-19–affected lung tissue. We applied correlation network–based approaches to deconvolve gene expression data from 46 areas of interest covering more than 62,000 cells within well-preserved lung samples from 3 patients. Despite substantial interpatient heterogeneity, we discovered evidence for a common immune-cell signaling circuit in areas of severe tissue that involves crosstalk between cytotoxic lymphocytes and pro-inflammatory macrophages. Expression of IFNG by cytotoxic lymphocytes was associated with induction of chemokines, including CXCL9, CXCL10, and CXCL11, which are known to promote the recruitment of CXCR3+ immune cells. The TNF superfamily members BAFF (TNFSF13B) and TRAIL (TNFSF10) were consistently upregulated in the areas with severe tissue damage. We used published spatial and single-cell SARS-CoV-2 data sets to validate our findings in the lung tissue from additional cohorts of patients with COVID-19. The resulting model of severe COVID-19 immune-mediated tissue pathology may inform future therapeutic strategies.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
64.5
作者：
COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium. Electronic address: julian.knight@well.ox.ac.uk;COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium
通讯作者：
COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
17.1
作者：
通讯作者：
--
影响因子：
64.8
作者：
Delorey TM;Ziegler CGK;Heimberg G;Normand R;Yang Y;Segerstolpe Å;Abbondanza D;Fleming SJ;Subramanian A;Montoro DT;Jagadeesh KA;Dey KK;Sen P;Slyper M;Pita-Juárez YH;Phillips D;Biermann J;Bloom-Ackermann Z;Barkas N;Ganna A;Gomez J;Melms JC;Katsyv I;Normandin E;Naderi P;Popov YV;Raju SS;Niezen S;Tsai LT;Siddle KJ;Sud M;Tran VM;Vellarikkal SK;Wang Y;Amir-Zilberstein L;Atri DS;Beechem J;Brook OR;Chen J;Divakar P;Dorceus P;Engreitz JM;Essene A;Fitzgerald DM;Fropf R;Gazal S;Gould J;Grzyb J;Harvey T;Hecht J;Hether T;Jané-Valbuena J;Leney-Greene M;Ma H;McCabe C;McLoughlin DE;Miller EM;Muus C;Niemi M;Padera R;Pan L;Pant D;Pe'er C;Pfiffner-Borges J;Pinto CJ;Plaisted J;Reeves J;Ross M;Rudy M;Rueckert EH;Siciliano M;Sturm A;Todres E;Waghray A;Warren S;Zhang S;Zollinger DR;Cosimi L;Gupta RM;Hacohen N;Hibshoosh H;Hide W;Price AL;Rajagopal J;Tata PR;Riedel S;Szabo G;Tickle TL;Ellinor PT;Hung D;Sabeti PC;Novak R;Rogers R;Ingber DE;Jiang ZG;Juric D;Babadi M;Farhi SL;Izar B;Stone JR;Vlachos IS;Solomon IH;Ashenberg O;Porter CBM;Li B;Shalek AK;Villani AC;Rozenblatt-Rosen O;Regev A
通讯作者：
Regev A