In summary, our single-cell analysis of LCH uncovered an unexpected degree of cellular, transcriptomic, and epigenomic heterogeneity among LCH cells, indicative of complex developmental hierarchies in LCH lesions. We confirmed the presence of proliferative LCH cells in all analyzed biopsies using IHC, and we defined an epigenomic and gene-regulatory basis of the different LCH-cell subsets by chromatin-accessibility profiling. 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. 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.
It occupies a hybrid position between cancers and inflammatory diseases, which makes it an attractive model for studying cancer development. cell histiocytosis (LCH) is a rare neoplasm predominantly affecting children. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria. 1 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
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