Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells
Samuel W. Lukowski,
Inga Rødahl,
Samuel Kelly,
Meihua Yu,
James Gotley,
Chenhao Zhou,
Susan Millard,
Stacey B. Andersen,
Angelika N. Christ,
Gabrielle Belz,
Ian H. Frazer,
Janin Chandra
Affiliations
Samuel W. Lukowski
The Institute for Molecular Bioscience, The University of Queensland, 4067, QLD, Australia; The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia
Inga Rødahl
The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia
Samuel Kelly
The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia
Meihua Yu
The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia
James Gotley
The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia
Chenhao Zhou
The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia
Susan Millard
Mater Research, Translational Research Institute, Woolloongabba, 4102 QLD, Australia
Stacey B. Andersen
The Institute for Molecular Bioscience, The University of Queensland, 4067, QLD, Australia
Angelika N. Christ
The Institute for Molecular Bioscience, The University of Queensland, 4067, QLD, Australia
Gabrielle Belz
The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia
Ian H. Frazer
The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia
Janin Chandra
The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia; Corresponding author
Summary: Conventional dendritic cells (cDCs) are traditionally subdivided into cDC1 and cDC2 lineages. Batf3 is a cDC1-required transcription factor, and we observed that Batf3−/− mice harbor a population of cDC1-like cells co-expressing cDC2-associated surface molecules. Using single-cell RNA sequencing with integrated cell surface protein expression (CITE-seq), we found that Batf3−/− mitotic immature cDC1-like cells showed reduced expression of cDC1 features and increased levels of cDC2 features. In wild type, we also observed a proportion of mature cDC1 cells expressing surface features characteristic to cDC2 and found that overall cDC cell state heterogeneity was mainly driven by developmental stage, proliferation, and maturity. We detected population diversity within Sirpa+ cDC2 cells, including a Cd33+ cell state expressing high levels of Sox4 and lineage-mixed features characteristic to cDC1, cDC2, pDCs, and monocytes. In conclusion, these data suggest that multiple cDC cell states can co-express lineage-overlapping features, revealing a level of previously unappreciated cDC plasticity.
