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Single-cell analysis of CD45+ cells from duodenal RCDII tissue

ABSTRACT: Single-cell analysis of CD45+ cells from duodenal RCDII tissue

PROVIDER: PRJNA802136 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17833484_1.fastq.gz	Fastqsanger.gz
	SRR17833484_2.fastq.gz	Fastqsanger.gz
	SRR17833485_1.fastq.gz	Fastqsanger.gz
	SRR17833485_2.fastq.gz	Fastqsanger.gz

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Single-cell analysis of CD45+ cells from duodenal RCDII tissue

Project description:Refractory Celiac Disease type II (RCDII) is a rare lymphoma in the small intestine characterized by a clonally expanded intra-epithelial iCD3+sCD3-CD7+CD56- aberrant cell population. However, RCDII pathogenesis is ill-defined. Here, we aimed at single-cell characterization of the innate and adaptive immune system in RCDII. Paired small intestinal and blood samples from 12 RCDII patients and 6 healthy controls were assessed by single-cell mass cytometry with a 39 cell surface marker antibody panel, designed to capture heterogeneity of the innate and adaptive immune system. A second single-cell mass cytometry panel which included transcription factors and immune checkpoints was used for analysis of paired samples from 5 RCDII patients. Single-cell RNA sequencing analysis was performed on duodenal samples from 2 RCDII patients. Finally, we developed a 40-marker imaging mass cytometry antibody panel to evaluate cell-cell interactions in duodenal biopsies of RCDII patients. We provide evidence for inter- and intra-tumoral cell heterogeneity within the duodenal and peripheral aberrant cell population present in RCDII. We observed that part of the aberrant cell population proliferated and observed co-localization of aberrant cells with CD163+ APCs in situ. Additionally, we observed phenotypic discrepancy between peripheral and duodenal aberrant cells. Novel high-dimensional technologies reveal substantial inter- and intra-tumoral heterogeneity in the aberrant cell population in RCDII. This may underlie variability in refractory disease status between patients and responsiveness to therapy, pointing to the need for personalized therapy in RCDII based on patient-specific immune profiles.

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