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Pan-Cancer Single-Cell Dissection Reveals Phenotypically Distinct B Cell Subtypes

ABSTRACT: Pan-Cancer Single-Cell Dissection Reveals Phenotypically Distinct B Cell Subtypes

PROVIDER: PRJNA975512 | ENA |

REPOSITORIES: ENA

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Pan-Cancer Single-Cell Dissection Reveals Phenotypically Distinct B Cell Subtypes

Project description:Characterizing the compositional and phenotypic characteristics of tumor-infiltrating B cells (TIBs) is important for advancing our understanding of their role in cancer development. Here, we establish a comprehensive resource of human B cells by integrating single-cell RNA sequencing data of B cells from 649 patients across 19 major cancer types. We demonstrate substantial heterogeneity in their total abundance and subtype composition and observe immunoglobulin G (IgG)-skewness of antibody-secreting cell isotypes. Moreover, we identify stress-response memory B cells and tumor-associated atypical B cells (TAABs), two tumor-enriched subpopulations with prognostic potential, shared in a pan-cancer manner. In particular, TAABs, characterized by a high clonal expansion level and proliferative capacity as well as by close interactions with activated CD4 T cells in tumors, are predictive of immunotherapy response. Our integrative resource depicts distinct clinically relevant TIB subsets, laying a foundation for further exploration of functional commonality and diversity of B cells in cancer.

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Single-cell RNA-Seq resolves phenotypically heterogeneous subtypes in systemic juvenile idiopathic arthritis (SJIA)

Project description:Systemic juvenile idiopathic arthritis (SJIA) is a clinically heterogenous systemic inflammatory disorder sometimes complicated by macrophage activation syndrome (MAS) and lung disease (LD), which are thought to be driven by IFN signaling. To identify cellular sources and novel gene programs underlying SJIA pathogenesis, we performed the first in-depth single-cell RNA Sequencing (scRNA-Seq) analysis of 21 SJIA, SJIA-LD, and SJIA-MAS patient PBMCs. To define novel heterogenous patient-subtypes associated with shared transcriptional responses and associate these with clinical and diagnostic metadata, we developed the tools UDON and SATAY-UDON. These tools identify hidden patient-subtypes, including a novel Complement and IFN signaling gene program expressed by SJIA-LD monocyte populations, unravel cellular sources of IFN signaling in SJIA-MAS as CD4 T cells and monocytic cell types, and identify a previously unknown role for platelets and S100 proteins as drivers of systemic inflammation. These data provide insights into new potential therapeutic targets for SJIA complications.

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Pan-modification profiling facilitates a cross-evolutionary dissection of the thermoregulated ribosomal epitranscriptome - extradata2

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