Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow

Andreas Schlitzer, V. Sivakamasundari, Jinmiao Chen, Hermi Rizal Bin Sumatoh, Jaring Schreuder, Josephine Lum, Benoit Malleret, Sanqian Zhang, Anis Larbi, Francesca Zolezzi, Laurent Renia, Michael Poidinger, Shalin Naik, Evan W. Newell, Paul Robson, Florent Ginhoux

Research output: Contribution to journalArticlepeer-review

421 Citations (Scopus)

Abstract

Mouse conventional dendritic cells (cDCs) can be classified into two functionally distinct lineages: the CD8α + (CD103 +) cDC1 lineage, and the CD11b + cDC2 lineage. cDCs arise from a cascade of bone marrow (BM) DC-committed progenitor cells that include the common DC progenitors (CDPs) and pre-DCs, which exit the BM and seed peripheral tissues before differentiating locally into mature cDCs. Where and when commitment to the cDC1 or cDC2 lineage occurs remains poorly understood. Here we found that transcriptional signatures of the cDC1 and cDC2 lineages became evident at the single-cell level from the CDP stage. We also identified Siglec-H and Ly6C as lineage markers that distinguished pre-DC subpopulations committed to the cDC1 lineage (Siglec-H ' ' Ly6C ' ' pre-DCs) or cDC2 lineage (Siglec-H ' ' Ly6C + pre-DCs). Our results indicate that commitment to the cDC1 or cDC2 lineage occurs in the BM and not in the periphery.

Original languageEnglish
Pages (from-to)718-728
Number of pages11
JournalNature Immunology
Volume16
Issue number7
DOIs
Publication statusPublished - 20 Jul 2015
Externally publishedYes

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