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Immune cells direct epithelial maturation during early human lung development


ABSTRACT: The adult human lung harbours a significant proportion of immune cells, which are known to play a crucial role in both normal lung homeostasis and pathogenesis. In this work, we collected CD45-enriched human lung cells from 6 to 22 week post conception (pcw) and built a single-cell transcriptome and proteome atlas. We showed a biphasic mode of immune cell development peaking at 8-9 and 20 pcw respectively. The developing immune cells potentially modulate the maturation of the epithelium through signalling molecules. We demonstrated using the lung organoid model that IL-1ß was required for epithelium differentiation. Overall, we provide a resource for the community of lung biologists and immunologists and provide insights on the interaction between the innate immune system and epithelium during fetal development.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: Josephine Barnes 

PROVIDER: E-MTAB-11528 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Early human lung immune cell development and its role in epithelial cell fate.

Barnes Josephine L JL   Yoshida Masahiro M   He Peng P   Worlock Kaylee B KB   Lindeboom Rik G H RGH   Suo Chenqu C   Pett J Patrick JP   Wilbrey-Clark Anna A   Dann Emma E   Mamanova Lira L   Richardson Laura L   Polanski Krzysztof K   Pennycuick Adam A   Allen-Hyttinen Jessica J   Herczeg Iván T IT   Arzili Romina R   Hynds Robert E RE   Teixeira Vitor H VH   Haniffa Muzlifah M   Lim Kyungtae K   Sun Dawei D   Rawlins Emma L EL   Oliver Amanda J AJ   Lyons Paul A PA   Marioni John C JC   Ruhrberg Christiana C   Tuong Zewen Kelvin ZK   Clatworthy Menna R MR   Reading James L JL   Janes Sam M SM   Teichmann Sarah A SA   Meyer Kerstin B KB   Nikolić Marko Z MZ  

Science immunology 20231215 90


Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry. At the embryonic stage, we  ...[more]

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