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RNA-seq of patients with aplastic anemia in the presence or absence of levamisole in vitro

ABSTRACT: RNA-seq of patients with aplastic anemia

PROVIDER: PRJEB54093 | ENA |

REPOSITORIES: ENA

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RNA-seq of patients with aplastic anemia in the presence or absence of levamisole in vitro

Project description:Bone marrow nucleated cells (BMNCs) from healthy donors and patients with non-severe aplastic anemia (NSAA) at the time of initial diagnosis were separated, and then co-cultured with or without 40 μg/mL levamisole (LMS) for 48 hours in vitro. Cells were harvested and total RNA were extracted. The sequencing assay were carried out using the Illumina HiSeq X platform and the data obtained were analyzed by following the Hisat2 protocol.

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RNA-seq of patients with aplastic anemia in the presence or absence of levamisole in vitro

Project description:RNA-seq of patients with aplastic anemia in the presence or absence of levamisole in vitro

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Single cell transcriptome from aplastic anemia (AA) and healthy donors [3' RNA-seq]

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Somatic mutations in lymphocytes in patients with immune-mediated aplastic anemia

Project description:In this study, we investigated somatic mutations of CD4+ and CD8+ T cells in patients with immune-mediated aplastic anemia (AA). To understand the role of mutations, we performed single-cell level analysis of 6 longitudinal samples of 2 AA patients carrying STAT3 or KRAS and other mutations in CD8+ T cells. The analysis was performed using V(D)J and 5' gene expression platform (10X Genomics). STAT3 mutated clone was clearly distinguishable from other CD8+ T cells and showed a cytotoxic phenotype, attenuated by successful immunosuppressive treatment. Our results suggest that somatic mutations in T cells can alter T cell phenotype warranting further investigation of their role in the pathogenesis of immune-mediated AA.

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Project description:Clonal hematopoiesis was investigated in patients with aplastic anemia using next-generation sequencing and single-nucleotide polymorphism (SNP) array-based karyotyping.

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Transcriptome analysis of HLA-DR(+) HSPCs and HLA-DR(-) HSPCs in aplastic anemia patients

Project description:HLA-DR-lacking HSPCs [HLA-DR(-) HSPCs] were detected in aplastic anemia (AA) patients with HLA-DR15. HLA-DR(-) HSPCs may evade the attack by CD4+ T-cells recognizing the autoantigen presented by HLA-DR15. The goal of this study is to clarify the immune escape mechanisms from antigen-specific T-cells by comparing the trranscriptome profile of HLA-DR(+) HSPCs and HLA-DR(-) HSPCs.

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Luspatercept with Immunosuppression Reducess Inflammation in Patients with Severe Aplastic Anemia by Inhibiting Monocyte Pyroptosis [RNA-Seq]

Project description:Aplastic anemia (AA) is a bone marrow failure disorder caused by diverse etiologies. AA pathogenesis involves aberrant immune activation and an imbalanced inflammatory bone marrow microenvironment. Previous studies have shown that inhibition of transforming growth factor-β (TGF-β) signaling in patients with AA can improve multilineage hematopoietic recovery and immune balance. This study is the first to demonstrate the synergistic mechanisms of TGF-β inhibitor luspatercept in combination with Cyclosporine and Eltrombopag for the treatment of severe aplastic anemia (SAA) by acting on monocytes. The aim was to explore the effects of the drug Luspatercept on monocyte cell lines by performing RNA-seq after treating the THP-1 cell line. Mechanistic investigations further showed luspatercept suppressed pyroptosis in monocytes, reshaping the immune microenvironment, and attenuating pro-inflammatory cytokine secretion and cytotoxic molecule expression in CD8+T cells. This groundbreaking study uncovers that Luspatercept can reduce inflammation and pyroptosis through multi-target immune modulation, which provides a novel therapeutic strategy for AA.

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