Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing
Artikel i vetenskaplig tidskrift, 2021
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.
Författare
Luca Mazzurana
Karolinska Institutet
Paulo Czarnewski
Stockholms universitet
Viktor Jonsson
Chalmers, Biologi och bioteknik, Systembiologi
Leif Wigge
Chalmers, Biologi och bioteknik, Systembiologi
Markus Ringnér
Lunds universitet
Teresa C. Williams
Karolinska Institutet
Avinash Ravindran
Karolinska universitetssjukhuset
Åsa K. Björklund
Uppsala universitet
Jesper Säfholm
Karolinska Institutet
Gunnar Nilsson
Karolinska universitetssjukhuset
Sven Erik Dahlén
Karolinska Institutet
Ann Charlotte Orre
Karolinska universitetssjukhuset
Mamdoh Al-Ameri
Karolinska universitetssjukhuset
Karolinska Institutet
Charlotte Höög
Karolinska Institutet
Charlotte Hedin
Karolinska universitetssjukhuset
Karolinska Institutet
Sylwester Szczegielniak
Karolinska universitetssjukhuset
Sven Almer
Karolinska Institutet
Karolinska universitetssjukhuset
Jenny Mjösberg
Karolinska Institutet
Cell Research
1001-0602 (ISSN) 17487838 (eISSN)
Vol. 31 5 554-568Ämneskategorier
Immunologi
Cell- och molekylärbiologi
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
DOI
10.1038/s41422-020-00445-x
PubMed
33420427