TY - JOUR TI - Single-cell analyses reveal the clonal and molecular aetiology of Flt3L-induced emergency dendritic cell development AU - Lin, Dawn S. AU - Tian, Luyi AU - Tomei, Sara AU - Amann-Zalcenstein, Daniela AU - Baldwin, Tracey M. AU - Weber, Tom S. AU - Schreuder, Jaring AU - Stonehouse, Olivia J. AU - Rautela, Jai AU - Huntington, Nicholas D. AU - Taoudi, Samir AU - Ritchie, Matthew E. AU - Hodgkin, Philip D. AU - Ng, Ashley P. AU - Nutt, Stephen L. AU - Naik, Shalin H. T2 - Nature Cell Biology AB - 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 transcriptome of individual HSPCs. We discover that Flt3L-responsive HSPCs maintain a proliferative ‘early progenitor’-like state, leading to the selective expansion of multiple transitional cDC1-primed progenitor stages that are marked by Irf8 expression. These findings define the mechanistic action of Flt3L through clonal tuning, which has important implications for other models of ‘emergency’ haematopoiesis. DA - 2021/03/01/ PY - 2021 DO - 10.1038/s41556-021-00636-7 DP - www.nature.com SP - 1 EP - 13 LA - en SN - 1476-4679 UR - https://www.nature.com/articles/s41556-021-00636-7 Y2 - 2021/03/02/00:31:59 ER -