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Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing

Mazzurana, Luca ; Czarnewski, Paulo ; Jonsson, Viktor ; Wigge, Leif ; Ringnér, Markus LU orcid ; Williams, Teresa C ; Ravindran, Avinash ; Björklund, Åsa K ; Säfholm, Jesper and Nilsson, Gunnar , et al. (2021) In Cell Research 31(5). p.554-568
Abstract

The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2+ and CRTH2- ILC2 with lung-specific signatures, which could... (More)

The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2+ and CRTH2- ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-δ rearrangement. Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Research
volume
31
issue
5
pages
15 pages
publisher
Science Press
external identifiers
  • pmid:33420427
  • scopus:85099083314
ISSN
1748-7838
DOI
10.1038/s41422-020-00445-x
language
English
LU publication?
yes
id
009c0123-8e47-4fc7-949e-fd2da1a6f9e8
date added to LUP
2021-01-12 23:02:01
date last changed
2024-05-17 01:55:47
@article{009c0123-8e47-4fc7-949e-fd2da1a6f9e8,
  abstract     = {{<p>The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2+ and CRTH2- ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-δ rearrangement. Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.</p>}},
  author       = {{Mazzurana, Luca and Czarnewski, Paulo and Jonsson, Viktor and Wigge, Leif and Ringnér, Markus and Williams, Teresa C and Ravindran, Avinash and Björklund, Åsa K and Säfholm, Jesper and Nilsson, Gunnar and Dahlén, Sven-Erik and Orre, Ann-Charlotte and Al-Ameri, Mamdoh and Höög, Charlotte and Hedin, Charlotte and Szczegielniak, Sylwester and Almer, Sven and Mjösberg, Jenny}},
  issn         = {{1748-7838}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{5}},
  pages        = {{554--568}},
  publisher    = {{Science Press}},
  series       = {{Cell Research}},
  title        = {{Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing}},
  url          = {{http://dx.doi.org/10.1038/s41422-020-00445-x}},
  doi          = {{10.1038/s41422-020-00445-x}},
  volume       = {{31}},
  year         = {{2021}},
}