HCA Data Explorer

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

Updated November 6, 2023

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.

Elo MadissoonWellcome Sanger Institute
Elo Madissoon1
Amanda Oliver1
Vitalii Kleshchevnikov1
Anna Wilbrey-Clark1
Krzysztof Polanski1
Ana Ribeiro Orsi1
Lira Mamanova1
Liam Bolt1
Nathan Richoz2
Rasa Elmentaite1
Patrick Pett1
Ni Huang1
Peng He1
Monika Dabrowska1
Sophie Pritchard1
Liz Tuck1
Elena Prigmore1
Andrew Knights1
Agnes Oszlanczi1
Adam Hunter1
Sara Vieira1
Minal Patel1
Nikitas Georgakopoulos3
Krishnaa Mahbubani3
Kourosh Saeb-Parsy3
Menna Clatworthy2
Omer Ali Bayraktar4
Oliver Stegle4
Natsuhiko Kumasaka4
Sarah Teichmann4
Kerstin Meyer4
1Wellcome Sanger Institute
2MRC Laboratory of Molecular Biology
3Cambridge NIHR Biomedical Research Centre
4Wellcome Sanger
Wei Kheng Teh

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/957261f7-2bd6-4358-a6ed-24ee080d5cfc
None
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Analysis Portals

None

Project Label

AdultLungElo

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

lung

Organ Part

5 organ parts

Selected Cell Types

bone marrow hematopoietic cell

Disease Status (Specimen)

normal

Disease Status (Donor)

2 disease statuses

Development Stage

human adult stage

Library Construction Method

6 library construction methods

Nucleic Acid Source

2 nucleic acid sources

Paired End

false

Analysis Protocol

analysisprotocol

File Format

7 file formats

Cell Count Estimate

193.1k

Donor Count

13
cloupe20 file(s)csv1 file(s)fastq.gz561 file(s)h5ad2 file(s)jpg17 file(s)tif3 file(s)xlsx1 file(s)