| Literature DB >> 33649477 |
Dawn S Lin1,2,3, Luyi Tian1,2,3,4, Sara Tomei1,2,3, Daniela Amann-Zalcenstein1,2,5, Tracey M Baldwin5,6, Tom S Weber1,2, Jaring Schreuder1, Olivia J Stonehouse2,3,4, Jai Rautela7,8, Nicholas D Huntington7,8, Samir Taoudi2,4, Matthew E Ritchie2,4, Philip D Hodgkin1,2, Ashley P Ng2,6, Stephen L Nutt1,2, Shalin H Naik9,10,11.
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 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.Entities:
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Year: 2021 PMID： 33649477 DOI： 10.1038/s41556-021-00636-7
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824