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
em En
| MEDLINE
| ID: mdl-33649477
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Células-Tronco Hematopoéticas
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Proliferação de Células
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Análise de Célula Única
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Transcriptoma
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RNA-Seq
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Hematopoese
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Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Nat Cell Biol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Austrália