Print Email Facebook Twitter Early-life compartmentalization of immune cells in human fetal tissues revealed by high-dimensional mass cytometry Title Early-life compartmentalization of immune cells in human fetal tissues revealed by high-dimensional mass cytometry Author Li, Na (Leiden University Medical Center) van Unen, Vincent (Leiden University Medical Center) Guo, Nannan (Leiden University Medical Center) Abdelaal, T.R.M. (TU Delft Pattern Recognition and Bioinformatics; Leiden University Medical Center) Somarakis, Antonios (Leiden University Medical Center) Eggermont, Jeroen (Leiden University Medical Center) Mahfouz, A.M.E.T.A. (Leiden University Medical Center) Chuva de Sousa Lopes, Susana 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) Date 2019 Abstract The human fetal immune system must protect the infant against the sudden exposure to a large variety of pathogens upon birth. While it is known that the fetal immune system develops in sequential waves, relatively little is known about the composition of the innate and adaptive immune system in the tissues. Here, we applied high-dimensional mass cytometry to profile the immune system in human fetal liver, spleen, and intestine. With Hierarchical Stochastic Neighbor Embedding (HSNE) we distinguished 177 distinct immune cell clusters, including both previously identified and novel cell clusters. PCA analysis indicated substantial differences between the compositions of the immune system in the different organs. Through dual t-SNE we identified tissue-specific cell clusters, which were found both in the innate and adaptive compartment. To determine the spatial location of tissue-specific subsets we developed a 31-antibody panel to reveal both the immune compartment and surrounding stromal elements through analysis of snap-frozen tissue samples with imaging mass cytometry. Imaging mass cytometry reconstructed the tissue architecture and allowed both the characterization and determination of the location of the various immune cell clusters within the tissue context. Moreover, it further underpinned the distinctness of the immune system in the tissues. Thus, our results provide evidence for early compartmentalization of the adaptive and innate immune compartment in fetal spleen, liver, and intestine. Together, our data provide a unique and comprehensive overview of the composition and organization of the human fetal immune system in several tissues. Subject Fetal intestineFetal liverFetal spleenHigh-dimensional analysisImaging mass cytometry (IMC)Immune compositionMass cytometry (CyTOF) To reference this document use: http://resolver.tudelft.nl/uuid:a3525330-b7a4-4ff4-ba8f-5744be55f7a2 DOI https://doi.org/10.3389/fimmu.2019.01932 Source Frontiers in Immunology, 10, 1-13 Part of collection Institutional Repository Document type journal article Rights © 2019 Na Li, Vincent van Unen, Nannan Guo, T.R.M. Abdelaal, Antonios Somarakis, Jeroen Eggermont, A.M.E.T.A. Mahfouz, Susana M. Chuva de Sousa Lopes, B.P.F. Lelieveldt, Frits Koning Files PDF fimmu_10_01932.pdf 4.53 MB Close viewer /islandora/object/uuid:a3525330-b7a4-4ff4-ba8f-5744be55f7a2/datastream/OBJ/view