A spatially resolved atlas of the human lung characterizes a gland-associated immune niche.
A spatially resolved atlas of the human lung characterizes a gland-associated immune niche.
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DOI：
10.1038/s41588-022-01243-4
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发表时间：
2023-01
期刊：
影响因子：
30.8
通讯作者：
Meyer, Kerstin B.
中科院分区：
文献类型：
--
作者：
Madissoon, Elo;Oliver, Amanda J.;Kleshchevnikov, Vitalii;Wilbrey-Clark, Anna;Polanski, Krzysztof;Richoz, Nathan;Orsi, Ana Ribeiro;Mamanova, Lira;Bolt, Liam;Elmentaite, Rasa;Pett, J. Patrick;Huang, Ni;Xu, Chuan;He, Peng;Dabrowska, Monika;Pritchard, Sophie;Tuck, Liz;Prigmore, Elena;Perera, Shani;Knights, Andrew;Oszlanczi, Agnes;Hunter, Adam;Vieira, Sara F.;Patel, Minal;Lindeboom, Rik G. H.;Campos, Lia S.;Matsuo, Kazuhiko;Nakayama, Takashi;Yoshida, Masahiro;Worlock, Kaylee B.;Nikolic, Marko Z.;Georgakopoulos, Nikitas;Mahbubani, Krishnaa T.;Saeb-Parsy, Kourosh;Bayraktar, Omer Ali;Clatworthy, Menna R.;Stegle, Oliver;Kumasaka, Natsuhiko;Teichmann, Sarah A.;Meyer, Kerstin B.
单细胞转录学已经使人类肺中的细胞类型/状态得到了前所未有的分辨，但它们的空间背景还没有被很好地定义。为了(重新)定义肺和呼吸道的组织结构，我们使用多组单细胞/核和空间转录组学(可在rungcell atlas.org上查询)深入剖析了健康人肺的五个近端到远端位置。利用计算数据集成和分析，我们超越了悬浮细胞范式，发现了宏观和微观解剖组织隔间，包括上皮、血管、间质和神经束微环境中以前未注释的细胞类型。我们鉴定了肺疾病中的支气管周围成纤维细胞并将其与肺疾病联系起来。重要的是，我们发现并验证了呼吸道粘膜下腺(SMG)中IgA浆细胞的生存利基。我们发现腺上皮细胞通过CCL28、APRIL和IL-6的表达来招募B细胞和IgA浆细胞，并促进局部的长寿和抗体的分泌。这一新的“腺体相关免疫利基”对呼吸健康有影响。对45个人肺样本的多组学分析突出了沿肺近端到远端轴的80种不同细胞类型，某些细胞类型显示疾病相关基因的丰富。还发现了呼吸道粘膜下腺(SMG)内表达IgA的浆细胞的免疫小生境。
Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture of lung and airways, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and spatial transcriptomics (queryable at lungcellatlas.org). Using computational data integration and analysis, we extend beyond the suspension cell paradigm and discover macro and micro-anatomical tissue compartments including previously unannotated cell types in the epithelial, vascular, stromal and nerve bundle micro-environments. We identify and implicate peribronchial fibroblasts in lung disease. Importantly, we discover and validate a survival niche for IgA plasma cells in the airway submucosal glands (SMG). We show that gland epithelial cells recruit B cells and IgA plasma cells, and promote longevity and antibody secretion locally through expression of CCL28, APRIL and IL-6. This new ‘gland-associated immune niche’ has implications for respiratory health. Multi-omics profiling of 45 human lung samples highlights 80 different cell types along the proximal to distal axis of the lung with certain cell types showing enrichment for disease-associated genes. An immune niche for IgA-expressing plasma cells within airway submucosal glands (SMG) is also identified.
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影响因子：
11.8
作者：
Elmentaite R;Ross ADB;Roberts K;James KR;Ortmann D;Gomes T;Nayak K;Tuck L;Pritchard S;Bayraktar OA;Heuschkel R;Vallier L;Teichmann SA;Zilbauer M
通讯作者：
Zilbauer M
影响因子：
3.9
作者：
Bochukova, Elena G.;Roscioli, Tony;Wilkie, Andrew O. M.
通讯作者：
Wilkie, Andrew O. M.
影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
DOI：
10.1126/science.abl5197
发表时间：
2022-05-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Domínguez Conde C;Xu C;Jarvis LB;Rainbow DB;Wells SB;Gomes T;Howlett SK;Suchanek O;Polanski K;King HW;Mamanova L;Huang N;Szabo PA;Richardson L;Bolt L;Fasouli ES;Mahbubani KT;Prete M;Tuck L;Richoz N;Tuong ZK;Campos L;Mousa HS;Needham EJ;Pritchard S;Li T;Elmentaite R;Park J;Rahmani E;Chen D;Menon DK;Bayraktar OA;James LK;Meyer KB;Yosef N;Clatworthy MR;Sims PA;Farber DL;Saeb-Parsy K;Jones JL;Teichmann SA
通讯作者：
Teichmann SA
影响因子：
15.3
作者：
Bowman, E P;Campbell, J J;Soler, D;Dong, Z;Manlongat, N;Picarella, D;Hardy, R R;Butcher, E C
通讯作者：
Butcher, E C