Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells
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 seque...
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doaj-d40a660dfb404f28a5f14a6069e10f152021-05-28T05:03:35ZengElsevieriScience2589-00422021-05-01245102402Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cellsSamuel W. Lukowski0Inga Rødahl1Samuel Kelly2Meihua Yu3James Gotley4Chenhao Zhou5Susan Millard6Stacey B. Andersen7Angelika N. Christ8Gabrielle Belz9Ian H. Frazer10Janin Chandra11The Institute for Molecular Bioscience, The University of Queensland, 4067, QLD, Australia; The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, AustraliaThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, AustraliaThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, AustraliaThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, AustraliaThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, AustraliaThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, AustraliaMater Research, Translational Research Institute, Woolloongabba, 4102 QLD, AustraliaThe Institute for Molecular Bioscience, The University of Queensland, 4067, QLD, AustraliaThe Institute for Molecular Bioscience, The University of Queensland, 4067, QLD, AustraliaThe 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, AustraliaThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, AustraliaThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004221003709ImmunologyCell BiologyTranscriptomics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells iScience Immunology Cell Biology Transcriptomics |
author_facet |
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 |
author_sort |
Samuel W. Lukowski |
title |
Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells |
title_short |
Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells |
title_full |
Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells |
title_fullStr |
Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells |
title_full_unstemmed |
Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells |
title_sort |
absence of batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells |
publisher |
Elsevier |
series |
iScience |
issn |
2589-0042 |
publishDate |
2021-05-01 |
description |
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. |
topic |
Immunology Cell Biology Transcriptomics |
url |
http://www.sciencedirect.com/science/article/pii/S2589004221003709 |
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