Microsynth single tube sequencing7/1/2023 ![]() Similarly, leukemogenesis is conceptualized as the multistage process for normal hematopoietic stem and progenitor cells (HSPCs) to become full-blown leukemic cells. Tumorigenesis, a process to accumulate enough genetic alterations for normal cells to be transformed into malignant cells, can take decades in patients. Hematopoietic stem and progenitor cell LSC, The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC21009 to YL and ZYGD22012 to YL), the Sichuan University Postdoctoral Interdisciplinary Innovation Fund to XC, the Post-Doctor Research Project, West China Hospital, Sichuan University (2023HXBH019 to BW and 2023HXBH033 to XC), the China Postdoctoral Science Foundation (2022M722272 to JX). All flow cytometry data for S1 Fig are deposited in the FlowRepository database under accession number FR-FCM-Z64U and FR-FCM-Z64T.įunding: This work was supported by the National Natural Science Foundation of China (82130007 to YL, 82170171 to CC), the Sichuan Science and Technology Program (2021YFS0027 to LC, 2020YFQ0059 to CC, 2018JZ0077 to YL), the 1.3.5. The analysis code can be found at GitHub ( ). This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All scRNA-seq and RNA-seq data in this study are deposited in NCBI Gene Expression Omnibus under accession number GSE142645. ![]() Received: OctoAccepted: MaPublished: May 2, 2023Ĭopyright: © 2023 Wu et al. PLoS Biol 21(5):Īcademic Editor: Connie J. ![]() (2023) Single-cell transcriptome analyses reveal critical roles of RNA splicing during leukemia progression. Our study emphasized the critical roles of RNA splicing in the full process of leukemogenesis.Ĭitation: Wu B, Chen X, Pan X, Deng X, Li S, Wang Z, et al. While the exon skipping product Tmem134β promoted the cell cycle, full-length Tmem134α delayed tumorigenesis. Exon 4 skipping of Tmem134 was identified in these cells. Among them, the Hsp90aa1 hi subpopulation was conserved in both human and mouse AML and associated with poor prognosis. In the late stage, PLCs acquired explosive heterogeneity through RNA alternative splicing. 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. Among them were splicing factors, which showed stage-specific prognosis for AML patients. We found that the Myc targets were gradually up-regulated along the trajectory. 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. 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.
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