Genomics

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Epigenomics and Single-cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis [ATAC-seq]


ABSTRACT: Langerhans cell histiocytosis (LCH) is a rare neoplasm predominantly affecting children. It occupies a characteristic hybrid position between cancers and inflammatory diseases, which makes it an attractive model for studying cancer development. To explore the molecular mecha-nisms underlying the pathophysiology of LCH and its characteristic clinical heterogeneity, we investi-gated the transcriptomic and epigenomic diversity in primary LCH lesions. Using single-cell RNA se-quencing, 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 pro-liferative LCH cells in all analysed biopsies using immunohistochemistry, and we defined the epigenomic and gene-regulatory basis of the different LCH cell subsets using chromatin profiling. In summary, our single-cell analysis of LCH uncovered an unexpected degree of cellular, transcriptomic, and epigenomic heterogeneity among LCH cells, reflecting complex developmental hierarchies in LCH lesions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE133785 | GEO | 2019/07/30

REPOSITORIES: GEO

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