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Distinct ontogenetic lineages dictate cDC2 heterogeneity
Carlos M Minutti1,2, Cécile Piot3, Mariana Pereira da Costa3
1Immunobiology Laboratory, The Francis Crick Institute, London, UK. carlos.minutti@research.fchampalimaud.org.
Nature Immunology
|February 13, 2024
Summary
Distinct mouse precursor populations give rise to conventional dendritic cell 2A (cDC2A) and cDC2B subtypes. This suggests these dendritic cell subsets are determined early in development, not by the tissue environment.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Conventional dendritic cells (cDCs) are diverse, including cDC1 and cDC2 populations.
- cDC2s are further subdivided (e.g., T-bet+ cDC2As, T-bet- cDC2Bs), but their relationship and developmental origins remain unclear.
- All cDCs originate from bone marrow progenitors called pre-cDCs.
Purpose of the Study:
- To investigate the relationship between different cDC2 subtypes.
- To determine if cDC2 subtypes represent distinct lineages or adaptable cell states.
- To identify distinct precursor populations for cDC2A and cDC2B subtypes.
Main Methods:
- Identification and characterization of distinct mouse pre-cDC2 subsets in bone marrow and peripheral tissues.
- Tracing the differentiation pathways of identified precursor subsets.
- Analysis of cell surface markers (Siglec-H, CD8α) and transcription factors (T-bet, LysM) to define subsets.
Main Results:
- Distinct pre-cDC2 subsets were identified in the bone marrow, biased towards cDC2A or cDC2B differentiation.
- A Siglec-H+ pre-cDC2A population gave rise to T-bet+ cDC2As, while a Siglec-H- fraction generated T-bet- cDC2Bs.
- cDC2A/cDC2B lineage specification was observed to begin in the bone marrow.
Conclusions:
- Conventional dendritic cell 2A and cDC2B subtypes are ontogenetically determined lineages.
- The differentiation pathways are established early in hematopoietic precursors, not dictated by the peripheral tissue environment.
- This clarifies the developmental origins and interrelationships of key cDC2 subsets.
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