A spatial multi-omics atlas of the human lung reveals a novel immune cell survival niche

• Published in: bioRxiv
• Main Authors: Elo Madissoon, Oliver, Amanda Jane, Kleshchevnikov, Vitalii, Wilbrey-Clark, Anna, Polanski, Krzysztof, Ribeiro Orsi, Ana Elisa, Lira Mamanova, Bolt, Liam, Pett, Jan Patrick, Huang, Ni, Elmentaite, Rasa, Richoz, Nathan, He, Peng, Dabrowska, Monika, Tuck, Elizabeth, Prigmore, Elena, Knights, Andrew, Oszlanczi, Agnes, Hunter, Adam, Pritchard, Sophie, Vieira, Sara Filipa, Patel, Minal, Mahbubani, Krishnaa, Georgakopoulos, Nikitas, Clatworthy, Menna, Stegle, Oliver, Omer Ali Bayraktar, Saeb-Parsy, Kourosh, Kumasaka, Natsuhiko, Teichmann, Sarah Amalia, Meyer, Kerstin B
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 27.11.2021
• Subjects: Cell survival; Chondrocytes; Fibroblasts; Immunoglobulin A; Lungs; Microenvironments; Peripheral nerves; Plasma cells; Schwann cells; Smooth muscle; Submucosal gland; Transcription; Transcriptomics
• DOI: 10.1101/2021.11.26.470108

Multiple distinct cell types of the human lung and airways have been defined by single cell RNA sequencing (scRNAseq). Here we present a multi-omics spatial lung atlas to define additional heterogeneity and novel cell types which we map back into the macro- and micro-anatomical tissue context to define functional tissue microenvironments. First, we have generated a single cell and nuclei RNA sequencing, VDJ-sequencing and Visium Spatial Transcriptomics data set from 5 different locations of the human lung and airways. Second, we define additional cell types/states, as well as spatially map novel and known human airway cell types, such as chondrocytes, submucosal gland (SMG) duct cells, distinct pericyte and smooth muscle subtypes, immune-recruiting fibroblasts, peribronchial and perichondrial fibroblasts, peripheral nerve associated fibroblasts and Schwann cells. Finally, we define a survival niche for IgA-secreting plasma cells at the SMG, comprising the newly defined epithelial SMG-Duct cells, and B and T lineage immune cells. Using our transcriptomic data for cell-cell interaction analysis, we propose a signalling circuit that establishes and supports this niche. Overall, we provide a transcriptional and spatial lung atlas with multiple novel cell types that allows for the study of specific tissue microenvironments such as the newly defined gland-associated lymphoid niche (GALN). Competing Interest Statement In the past three years, SAT has received remuneration for consulting and Scientific Advisory Board Membership from Genentech, Roche, Biogen, GlaxoSmithKline, Foresite Labs and Qiagen. SAT is a co-founder, board member and holds equity in Transition Bio.