Summary

In humans, conventional dendritic cells (cDCs) exist as two unique populations characterized by expression of CD1c and CD141. cDCs arise from increasingly restricted but well-defined bone marrow progenitors that include the common DC progenitor that differentiates into the pre-cDC, which is the direct precursor of cDCs. In this study, we show that pre-cDCs in humans are heterogeneous, consisting of two distinct populations of precursors that are precommitted to become either CD1c+ or CD141+ cDCs. The two groups of lineage-primed precursors can be distinguished based on differential expression of CD172a. Both subpopulations of pre-cDCs arise in the adult bone marrow and can be found in cord blood and adult peripheral blood. Gene expression analysis revealed that CD172a+ and CD172a- pre-cDCs represent developmentally discrete populations that differentially express lineage-restricted transcription factors. A clinical trial of Flt3L injection revealed that this cytokine increases the number of both CD172a- and CD172a+ pre-cDCs in human peripheral blood.

Overall design

RNA seq libraries from 957 single cells were prepared using the SMART-Seq 2 protocol (Picelli et al., 2013); 341 Blood pre-cDC (Blood pre-cDC_S* data columns in the expMatrix.txt); 452 CB pre-cDC (CB pre-cDC_S* data columns in the expMatrix.txt); 87 CD141+ cDC (blood_bdca3_S* data columns in the expMatrix.txt); 77 CD1c+ cDC (blood_bdca1_S* data columns in the expMatrix.txt)

Contributors

Gaëlle Breton 1, Shiwei Zheng 2 3, Renan Valieris 4, Israel Tojal da Silva 4, Rahul Satija 2 3, Michel C Nussenzweig 5 6

Contact

gbreton@rockefeller.edu.(Gaëlle Breton )