Mass cytometry reveals innate lymphoid cell differentiation pathways in the human fetal intestine

Mass cytometry reveals innate lymphoid cell differentiation pathways in the human fetal intestine

Li, Na (Leiden University Medical Center)
van Unen, Vincent (Leiden University Medical Center)
Höllt, T. (TU Delft Computer Graphics and Visualisation; Leiden University Medical Center)
Thompson, Allan (Leiden University Medical Center)
van Bergen, Jeroen (Leiden University Medical Center)
Pezzotti, N. (TU Delft Computer Graphics and Visualisation)
Eisemann, E. (TU Delft Computer Graphics and Visualisation)
Vilanova Bartroli, A. (TU Delft Computer Graphics and Visualisation)
Chuva de Sousa Lopes, S.M. (Leiden University Medical Center)
Lelieveldt, B.P.F. (TU Delft Pattern Recognition and Bioinformatics; Leiden University Medical Center)
Koning, Frits (Leiden University Medical Center)

2018

Innate lymphoid cells (ILCs) are abundant in mucosal tissues and involved in tissue homeostasis and barrier function. Although several ILC subsets have been identified, it is unknown if additional heterogeneity exists, and their differentiation pathways remain largely unclear. We applied mass cytometry to analyze ILCs in the human fetal intestine and distinguished 34 distinct clusters through a t-SNE-based analysis. A lineage (Lin)^-CD7⁺CD127^-CD45RO⁺CD56⁺ population clustered between the CD127⁺ ILC and natural killer (NK) cell subsets, and expressed diverse levels of Eomes, T-bet, GATA3, and RORγt. By visualizing the dynamics of the t-SNE computation, we identified smooth phenotypic transitions from cells within the Lin^-CD7⁺CD127^-CD45RO⁺CD56⁺ cluster to both the NK cells and CD127⁺ ILCs, revealing potential differentiation trajectories. In functional differentiation assays, the Lin^-CD7⁺CD127^-CD45RO⁺CD56⁺CD8a^- cells could develop into CD45RA⁺ NK cells and CD127⁺RORγt⁺ ILC3-like cells. Thus, we identified a previously unknown intermediate innate subset that can differentiate into ILC3 and NK cells.

http://resolver.tudelft.nl/uuid:c4fd8633-fdd1-4109-9933-4b61b5bfe17d

https://doi.org/10.1084/jem.20171934

0022-1007

The Journal of Experimental Medicine, 215 (5), 1383-1396

Institutional Repository

journal article

© 2018 Na Li, Vincent van Unen, T. Höllt, Allan Thompson, Jeroen van Bergen, N. Pezzotti, E. Eisemann, A. Vilanova Bartroli, S.M. Chuva de Sousa Lopes, B.P.F. Lelieveldt, Frits Koning