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

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

PROVIDER: PRJNA552543 | ENA |

REPOSITORIES: ENA

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Epigenomics and Single-cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis

Project description:Epigenomics and Single-cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis

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

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

Project description: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.

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

Project description: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 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 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.

2019-07-30 | GSE133704 | GEO

Epigenomics and Single-Cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis.

Project description:Langerhans cell histiocytosis (LCH) is a rare neoplasm predominantly affecting children. It occupies a hybrid position between cancers and inflammatory diseases, which makes it 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 analyzed biopsies using IHC, 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 uncovered an unexpected degree of cellular, transcriptomic, and epigenomic heterogeneity among LCH cells, indicative of complex developmental hierarchies in LCH lesions. SIGNIFICANCE: 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 personalizing therapy.See related commentary by Gruber et al., p. 1343.This article is highlighted in the In This Issue feature, p. 1325.

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Notch is active in Langerhans Cell Histiocytosis and confers pathognomonic features on dendritic cells.

Project description:Langerhans cell histiocytosis (LCH) is a disease characterized by the accumulation of eponymous CD1a+ Langerin+ Langerhans-cell (LC)-like dendritic cells (DC) of largely unknown origin. Here we have performed comparative transcriptome analysis of highly purified CD207+/CD1a+ Langerhans cell histiocytosis (LCH) cells derived from different locations and disease courses and three major human dendritic cell lineages: epidermal Langerhans cells, myeloid dendritic cells (mDC1) and plasmacytoid dendritic cells (pDC) in order to investigate the relationship between LCH cells and naturally occurring dendritic cells. Data obtained indicate that LCH cells form a distinct DC entity. Furthermore, we have identified transcripts that are uniquely expressed by LCH cells in comparison to LC, mDC1, and pDC, and induce LCH-specific features in human DC. Primary cells were isolated from peripheral blood (mDC1 and pDC), skin (epidermal Langerhans cells) and CD207+/CD1a+ Langerhans cell histiocytosis (LCH) cells derived from different locations. RNA was isolated from these cells ex vivo.

2012-10-24 | E-GEOD-35340 | biostudies-arrayexpress

JAG2 signaling induces differentiation of CD14+ monocytes into Langerhans Cell Histiocytosis-like cells

Project description:This study aims to identify the cell of origin of Langerhans Cell Histiocytosis and the molecular mechanisms of its pathogenesis.

2018-07-29 | GSE114181 | GEO

Notch is active in Langerhans Cell Histiocytosis and confers pathognomonic features on dendritic cells.

2012-10-24 | GSE35340 | GEO

Epigenomics and Single-cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-07-30 | GSE133706 | GEO

Epigenomics and Single-cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis

| EGAS00001003822 | EGA