Grant Awarded in 2017

Mapping the heterogeneity of Langerhans cell histiocytosis using single-cell analysis

Principal Investigator
Florent Ginhoux
Singapore Immunology Network (SIgN) / A*STAR

Date of Award

December 2017

Amount of Award

Layperson Summary

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder characterized by inflammatory cell infiltrates in tissues such as the bones and skin. However, LCH clinical manifestation is highly heterogeneous, ranging from mild to life-threatening disease; affecting single organ system or multiple organs. Although BRAF p.V600E mutation (leading to the activation of the MAPK pathway, known to be oncogenic in multiple human cancers) have been reported in LCH cells and thought to be a major driver in the disease, not all accumulating LCH cells exhibit the BRAF p.V600E mutation suggesting that other mechanisms are involved. Here, we propose to comprehensively map LCH cell heterogeneity using single cell analysis of LCH cells. This means that we will measure biologically relevant signals for each single cells that will not be masked by usual bulk average information that actual techniques provide. We will profile LCH single cells from the blood and affected tissues from different donors using single-cell genomic (DNA level), single-cell transcriptomic (RNA level) and mass cytometry (Protein level).

Relevance: We hope to unravel new cell LCH subpopulations that have not yet been discovered and that could explain the why a lot of LCH cells that are supposed to be driving the disease do not exhibit the BRAF p.V600E mutation, suggesting that other mechanisms are involved. This unprecedented knowledge at the single cell level of LCH cells will allow the discovery of new molecules and pathways involved in the immunopathogenesis of this disease.

Potentials benefits for histiocytosis patients: This, in turn, will provide a translational platform for the improvement of diagnostics, monitoring, and identification of potential treatment targets in the clinic. Dissecting LCH biology on a single cell level may lead to the improvement of LCH diagnosis, monitoring, as well as the development of new treatment strategies targeting certain aspects of the mononuclear myeloid cell compartment.

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