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• W3136194453 abstract "Abstract Aplastic anemia (AA) is a T cell–mediated autoimmune disorder of the hematopoietic system manifested by severe depletion of the hematopoietic stem and progenitor cells (HSPCs). Nonetheless, our understanding of the complex relationship between HSPCs and T cells is still obscure, mainly limited by techniques and the sparsity of HSPCs in the context of bone marrow failure. Here we performed single-cell transcriptome analysis of residual HSPCs and T cells to identify the molecular players from patients with AA. We observed that residual HSPCs in AA exhibited lineage-specific alterations in gene expression and transcriptional regulatory networks, indicating a selective disruption of distinct lineage-committed progenitor pools. In particular, HSPCs displayed frequently altered alternative splicing events and skewed patterns of polyadenylation in transcripts related to DNA damage and repair, suggesting a likely role in AA progression to myelodysplastic syndromes. We further identified cell type–specific ligand-receptor interactions as potential mediators for ongoing HSPCs destruction by T cells. By tracking patients after immunosuppressive therapy (IST), we showed that hematopoiesis remission was incomplete accompanied by IST insensitive interactions between HSPCs and T cells as well as sustained abnormal transcription state. These data collectively constitute the transcriptomic landscape of disrupted hematopoiesis in AA at single-cell resolution, providing new insights into the molecular interactions of engaged T cells with residual HSPCs and render novel therapeutic opportunities for AA." @default.
• W3136194453 created "2021-03-29" @default.
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• W3136194453 date "2021-03-24" @default.
• W3136194453 modified "2023-10-10" @default.
• W3136194453 title "Single-cell transcriptomics dissects hematopoietic cell destruction and T-cell engagement in aplastic anemia" @default.
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• W3136194453 doi "https://doi.org/10.1182/blood.2020008966" @default.
• W3136194453 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8349468" @default.
• W3136194453 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33763704" @default.
• W3136194453 hasPublicationYear "2021" @default.
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