Single-cell atlas of LCH

Single-cell atlas of Langerhans cell histiocytosis

Single-cell atlas of LCH

Langerhans cell histiocytosis (LCH) is a rare neoplasm predominantly affecting children. It occupies a hybrid position between cancers and inflammatory diseases, and it provides an attractive model for studying cancer development. To explore the molecular mechanisms underlying the pathophysiology of LCH and its characteristic clinical heterogeneity, we investigated the transcriptomic and epigenomic diversity in primary LCH lesions. Using single-cell RNA sequencing, we identified multiple recurrent types of LCH cells within these biopsies, including putative LCH progenitor cells and several subsets of differentiated LCH cells. We confirmed the presence of proliferative LCH cells in all analysed biopsies using immunohistochemistry, and we defined an epigenomic and gene regulatory basis of the different LCH cell subsets by chromatin accessibility profiling. In summary, our single-cell analysis of LCH un-covered an unexpected degree of cellular, transcriptomic, and epigenomic heterogeneity among LCH cells, indicative of complex developmental hierarchies in LCH lesions.

This study sketches a molecular portrait of LCH lesions by combining single-cell transcriptomics with epigenome profiling. We uncovered extensive cellular heterogeneity, explained in part by an intrinsic developmental hierarchy of LCH cells. Our findings provide new insights and hypotheses for advancing LCH research and a starting point for personalising therapy.

Publication

Epigenomics and single-cell sequencing define a developmental hierarchy in Langerhans cell histiocytosis

Epigenomics and single-cell sequencing define a developmental hierarchy in Langerhans cell histiocytosis

Halbritter F*, Farlik M*, Schwentner R, Jug G, Fortelny N, Schnöller T, Pisa H, Schuster LC, Reinprecht A, Czech T, Gojo J, Holter W, Minkov M, Bauer WM, Simonitsch-Klupp I, Bock C*, Hutter C*

Cancer Discovery  9, 1406-1421 (2019). DOI: 10.1158/2159-8290.CD-19-0138

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* shared first or shared senior authorship