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人类肺部的空间分辨率图谱定义出一个腺体相关的免疫微环境特征
2022-12-24 10:54
来源：小柯机器人

英国威康桑格研究所Kerstin B. Meyer等研究人员合作发现，人类肺部的空间分辨率图谱定义出一个腺体相关的免疫微环境特征。该项研究成果于2022年12月21日在线发表在《自然—遗传学》杂志上。

为了（重新）定义肺和气道的组织结构，研究人员使用多组学单细胞/细胞核和空间转录组学（可在lungcellatlas.org查询）深入分析了健康人肺的五个近端到远端位置。利用计算数据的整合和分析，研究人员超越了悬浮细胞的范式，发现了宏观和微观的解剖组织区间，包括上皮、血管、基质和神经束微环境中以前未被命名的细胞类型。研究人员确定了支气管周围的成纤维细胞并将其与肺部疾病联系起来。
 
重要的是，研究人员发现并验证了气道粘膜下腺体（SMG）中IgA浆细胞的微环境。结果表明，腺体上皮细胞招募B细胞和IgA浆细胞，并通过表达CCL28、APRIL和IL-6促进长期和局部抗体分泌。这种新的“腺体相关免疫微环境”对呼吸系统健康有影响。
 
据介绍，单细胞转录组学能够对人类肺部的细胞类型/状态进行空前的解析，但它们的空间背景却不太明确。
 
附：英文原文

Title: A spatially resolved atlas of the human lung characterizes a gland-associated immune niche

Author: Madissoon, Elo, Oliver, Amanda J., Kleshchevnikov, Vitalii, Wilbrey-Clark, Anna, Polanski, Krzysztof, Richoz, Nathan, Ribeiro Orsi, Ana, 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., Nikoli, 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.

Issue&Volume: 2022-12-21

Abstract: 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.

DOI: 10.1038/s41588-022-01243-4

Source: https://www.nature.com/articles/s41588-022-01243-4

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex


本期文章：《自然—遗传学》：Online/在线发表

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