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Distinct ontogenetic lineages dictate cDC2 heterogeneity.

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journal contribution
posted on 2024-03-06, 14:07 authored by Carlos M Minutti, Cécile Piot, Mariana Pereira da Costa, Probir Chakravarty, Neil Rogers, Hector Huerga Encabo, Ana Cardoso, Jane Loong, Gilles Bessou, Cyrille Mionnet, Jean Langhorne, Dominique Bonnet, Marc Dalod, Elena Tomasello, Caetano Reis e Sousa
Conventional dendritic cells (cDCs) include functionally and phenotypically diverse populations, such as cDC1s and cDC2s. The latter population has been variously subdivided into Notch-dependent cDC2s, KLF4-dependent cDC2s, T-bet+ cDC2As and T-bet- cDC2Bs, but it is unclear how all these subtypes are interrelated and to what degree they represent cell states or cell subsets. All cDCs are derived from bone marrow progenitors called pre-cDCs, which circulate through the blood to colonize peripheral tissues. Here, we identified distinct mouse pre-cDC2 subsets biased to give rise to cDC2As or cDC2Bs. We showed that a Siglec-H+ pre-cDC2A population in the bone marrow preferentially gave rise to Siglec-H- CD8α+ pre-cDC2As in tissues, which differentiated into T-bet+ cDC2As. In contrast, a Siglec-H- fraction of pre-cDCs in the bone marrow and periphery mostly generated T-bet- cDC2Bs, a lineage marked by the expression of LysM. Our results showed that cDC2A versus cDC2B fate specification starts in the bone marrow and suggest that cDC2 subsets are ontogenetically determined lineages, rather than cell states imposed by the peripheral tissue environment.


Crick (Grant ID: CC2027, Grant title: Bonnet CC2027) Crick (Grant ID: CC2079, Grant title: Langhorne CC2079) Crick (Grant ID: CC2090, Grant title: Reis e Sousa CC2090) Crick (Grant ID: CC1107, Grant title: STP Bioinformatics & Biostatistics) Crick (Grant ID: CC2088, Grant title: Kassiotis CC2088) European Research Council (Grant ID: 786674 - DCPOIESIS, Grant title: ERC 786674 - DCPOIESIS) Wellcome Trust (Grant ID: 106973/Z/15/Z, Grant title: WT 106973/Z/15/Z) Wellcome Trust (Grant ID: 223136/Z/21/Z, Grant title: WT 223136/Z/21/Z)


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