Spatially resolved deconvolution of the fibrotic niche in lung fibrosis.
Spatially resolved deconvolution of the fibrotic niche in lung fibrosis.
复制标题
DOI：
10.1016/j.celrep.2022.111230
复制
发表时间：
2022-08-16
期刊：
影响因子：
8.8
通讯作者：
Jones, Mark G.
中科院分区：
文献类型：
--
作者：
Eyres, Michael;Bell, Joseph A.;Davies, Elizabeth R.;Fabre, Aurelie;Alzetani, Aiman;Jogai, Sanjay;Marshall, Ben G.;Johnston, David A.;Xu, Zijian;Fletcher, Sophie, V;Wang, Yihua;Marshall, Gayle;Davies, Donna E.;Offer, Emil;Jones, Mark G.
人类肺纤维化的一个定义性病理特征是局部组织异质性，这对通常丢失空间信息的转录组学研究的解释提出了挑战。在这里，我们研究空间基因表达诊断组织使用数字分析技术。我们确定不同的，区域特异性的基因表达签名以及共享的基因签名。通过与单细胞数据的整合，我们在空间上映射了纤维化小生境内和远离纤维化小生境的细胞组成，即使在形态学保存的肺中，也显示了稳态和病理细胞群的离散变化，而通过配体-受体分析，我们研究了纤维化小生境内的细胞串扰。我们通过生物信息学、组织和体外分析证实了这一发现，确定肺泡上皮细胞中NF κ B抑制剂zeta的缺失使TGFβ/IL-6信号传导轴失调，这可能损害对环境应激的稳态反应。因此，空间分辨去卷积推进了对人类肺纤维化中细胞组成和微环境的理解。人肺纤维化发生的基因表达谱在纤维化小生境中稳态和病理细胞群的变化成纤维细胞灶内骨形态发生特征的鉴定肺泡上皮细胞NF κ B/IκB B β表达的缺失使IL-6轴失调Eyres et al.生成人类肺组织的空间转录组图，并显示肺纤维化中这是如何被扰乱的。他们通过纤维化微环境中复杂细胞串扰的证据来识别细胞群体的获得和损失。
A defining pathological feature of human lung fibrosis is localized tissue heterogeneity, which challenges the interpretation of transcriptomic studies that typically lose spatial information. Here we investigate spatial gene expression in diagnostic tissue using digital profiling technology. We identify distinct, region-specific gene expression signatures as well as shared gene signatures. By integration with single-cell data, we spatially map the cellular composition within and distant from the fibrotic niche, demonstrating discrete changes in homeostatic and pathologic cell populations even in morphologically preserved lung, while through ligand-receptor analysis, we investigate cellular cross-talk within the fibrotic niche. We confirm findings through bioinformatic, tissue, and in vitro analyses, identifying that loss of NFKB inhibitor zeta in alveolar epithelial cells dysregulates the TGFβ/IL-6 signaling axis, which may impair homeostatic responses to environmental stress. Thus, spatially resolved deconvolution advances understanding of cell composition and microenvironment in human lung fibrogenesis. Spatial gene expression profiles for human lung fibrogenesis Changes in homeostatic and pathologic cell populations in the fibrotic niche Identification of a bone morphogenesis signature within fibroblastic foci Loss of alveolar epithelial NFKBIZ/IκBζ expression dysregulates the IL-6 axis Eyres et al. generate a spatial transcriptomic map of human lung tissue and show how this is perturbed in pulmonary fibrosis. They identify gain and loss of cell populations with evidence of complex cellular cross-talk within the fibrotic microenvironment.
登录
查看更多内容
感染在间质性肺部疾病中的作用：综述。
影响因子：
9.6
作者：
Azadeh N;Limper AH;Carmona EM;Ryu JH
通讯作者：
Ryu JH
DOI：
10.1164/rccm.202007-2794oc
发表时间：
2020-12-15
影响因子：
24.7
作者：
Drake TM;Docherty AB;Harrison EM;Quint JK;Adamali H;Agnew S;Babu S;Barber CM;Barratt S;Bendstrup E;Bianchi S;Villegas DC;Chaudhuri N;Chua F;Coker R;Chang W;Crawshaw A;Crowley LE;Dosanjh D;Fiddler CA;Forrest IA;George PM;Gibbons MA;Groom K;Haney S;Hart SP;Heiden E;Henry M;Ho LP;Hoyles RK;Hutchinson J;Hurley K;Jones M;Jones S;Kokosi M;Kreuter M;MacKay LS;Mahendran S;Margaritopoulos G;Molina-Molina M;Molyneaux PL;O'Brien A;O'Reilly K;Packham A;Parfrey H;Poletti V;Porter JC;Renzoni E;Rivera-Ortega P;Russell AM;Saini G;Spencer LG;Stella GM;Stone H;Sturney S;Thickett D;Thillai M;Wallis T;Ward K;Wells AU;West A;Wickremasinghe M;Woodhead F;Hearson G;Howard L;Baillie JK;Openshaw PJM;Semple MG;Stewart I;Jenkins RG;ISARIC4C Investigators
通讯作者：
ISARIC4C Investigators
影响因子：
4.6
作者：
Ahn, Jae-Hee;Cho, Jaewon;Ko, Hyun-Jeong
通讯作者：
Ko, Hyun-Jeong
DOI：
10.1164/rccm.202008-3093oc
发表时间：
2021-07-15
影响因子：
24.7
作者：
Huang, Yong;Oldham, Justin M.;Noth, Imre
通讯作者：
Noth, Imre
DOI：
10.1073/pnas.1320318110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Feig, Christine;Jones, James O.;Fearon, Douglas T.
通讯作者：
Fearon, Douglas T.