Journal article

Single-cell analyses reveal the clonal and molecular aetiology of Flt3L-induced emergency dendritic cell development

Dawn S Lin, Luyi Tian, Sara Tomei, Daniela Amann-Zalcenstein, Tracey M Baldwin, Tom S Weber, Jaring Schreuder, Olivia J Stonehouse, Jai Rautela, Nicholas D Huntington, Samir Taoudi, Matthew E Ritchie, Philip D Hodgkin, Ashley P Ng, Stephen L Nutt, Shalin H Naik

NATURE CELL BIOLOGY | NATURE RESEARCH | Published : 2021

Abstract

Regulation of haematopoietic stem and progenitor cell (HSPC) fate is crucial during homeostasis and under stress conditions. Here we examine the aetiology of the Flt3 ligand (Flt3L)-mediated increase of type 1 conventional dendritic cells (cDC1s). Using cellular barcoding we demonstrate this occurs through selective clonal expansion of HSPCs that are primed to produce cDC1s and not through activation of cDC1 fate by other HSPCs. In particular, multi/oligo-potent clones selectively amplify their cDC1 output, without compromising the production of other lineages, via a process we term tuning. We then develop Divi-Seq to simultaneously profile the division history, surface phenotype and transcr..

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Grants

Awarded by National Health and Medical Research Council (NHMRC), Australia


Awarded by Victorian Cancer Agency (VCA)


Funding Acknowledgements

We thank the Walter and Eliza Hall Bioservices facility, FACS laboratory and S. Wilcox for technical support. We thank S. Heinzel, F. Vaillant and J. Visvader for providing critical reagents as well as technical and intellectual advice. We thank K. Shortman for insightful discussions and critical feedback on the paper. This work was supported by grants from the National Health and Medical Research Council (NHMRC), Australia (grant nos GNT1062820, GNT1100033, GNT1101378, GNT1124812 and GNT1145184), the Australia Research Council's special initiative Stem Cells Australia, and through a funded research agreement with Gilead Inc. P.D.H is supported by an NHMRC fellowship. J.R. is supported by a Victorian Cancer Agency (VCA) grant (grant no. ECSG18020).