Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing
(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.
(Less)
- author
- organization
- publishing date
- 2021-05-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cell Research
- volume
- 31
- issue
- 5
- pages
- 15 pages
- publisher
- Science Press
- external identifiers
-
- scopus:85099083314
- pmid:33420427
- 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
- 2024-09-19 14:00:08
@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}}, }