Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells

iScience

Inga Rødahl¹  Janin Chandra²  Stacey B. Andersen³  Samuel W. Lukowski⁴  Angelika N. Christ⁴  Gabrielle Belz⁴  James Gotley⁵  Ian H. Frazer⁵  Samuel Kelly⁵  Meihua Yu⁵  Chenhao Zhou⁵  Susan Millard⁵ 

[1] 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;Mater Research, Translational Research Institute, Woolloongabba, 4102 QLD, Australia;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;

关键词: Immunology;    Cell Biology;    Transcriptomics;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown