ArticlePLoS biology2023
Single-cell transcriptome analyses reveal critical roles of RNA splicing during leukemia progression.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- Splicing factor mutations clearance and outcomes in clonal myeloid neoplasms: a referral center experience.Annals of hematology · 2026Article
- Diving into the transcriptional landscape of leukemic stem cells in acute myeloid leukemia at single-cell resolution.Journal of cancer research and clinical oncology · 2026Review
- BCLAF1 links RNA splicing to ATF4-dependent metabolic adaptation in acute myeloid leukemia.bioRxiv : the preprint server for biology · 2026Article
- Unraveling the impact of crizotinib to promote megakaryopoiesis for alleviating thrombocytopenia in myelodysplastic neoplasms.Leukemia · 2025Article
- HemaScope: A Tool for Analyzing Single-cell and Spatial Transcriptomics Data of Hematopoietic Cells.Genomics, proteomics & bioinformatics · 2025Article
- Neurotransmission Sex Dichotomy in the Rat Hypothalamic Paraventricular Nucleus in Healthy and Infantile Spasm Model.Current issues in molecular biology · 2025Article
- Article
- Emerging strategies to investigate the biology of early cancer.Nature reviews. Cancer · 2024Review
- Review
- Decoding leukemia at the single-cell level: clonal architecture, classification, microenvironment, and drug resistance.Experimental hematology & oncology · 2024Review
- DNMT3A mutation promotes leukemia development through NAM-NAD metabolic reprogramming.Journal of translational medicine · 2023Article
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leukemogenesis is proposed to be a multistep process by which normal hematopoietic stem and progenitor cells are transformed into full-blown leukemic cells, the details of which are not fully understood. Here, we performed serial single-cell transcriptome analyses of preleukemic and leukemic cells (PLCs) and constructed the cellular and molecular transformation trajectory in a Myc-driven acute myeloid leukemia (AML) model in mice, which represented the transformation course in patients. We found that the Myc targets were gradually up-regulated along the trajectory. Among them were splicing factors, which showed stage-specific prognosis for AML patients. Furthermore, we dissected the detailed gene network of a tipping point for hematopoietic stem and progenitor cells (HSPCs) to generate initiating PLCs, which was characterized by dramatically increased splicing factors and unusual RNA velocity. In the late stage, PLCs acquired explosive heterogeneity through RNA alternative splicing. Among them, the Hsp90aa1hi subpopulation was conserved in both human and mouse AML and associated with poor prognosis. Exon 4 skipping of Tmem134 was identified in these cells. While the exon skipping product Tmem134β promoted the cell cycle, full-length Tmem134α delayed tumorigenesis. Our study emphasized the critical roles of RNA splicing in the full process of leukemogenesis.
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Registered trials
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