Single-cell analyses reveal the clonal and molecular aetiology of Flt3L-induced emergency dendritic cell development.
Nat Cell Biol
; 23(3): 219-231, 2021 03.
Article
en En
| MEDLINE
| ID: mdl-33649477
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Células Madre Hematopoyéticas
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Proliferación Celular
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Análisis de la Célula Individual
/
Transcriptoma
/
RNA-Seq
/
Hematopoyesis
/
Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nat Cell Biol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Australia