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Single-cell transcriptome analyses reveal critical roles of RNA splicing during leukemia progression.
Wu, Baohong; Chen, Xuelan; Pan, Xiangyu; Deng, Xintong; Li, Shujun; Wang, Zhongwang; Wang, Jian; Liao, Dan; Xu, Jing; Chen, Mei; Zhao, Chengjian; Xue, Zhihong; Wang, Yuan; Niu, Ting; Lin, Jingwen; Chen, Lu; Liu, Yu; Chen, Chong.
Afiliación
  • Wu B; Department of Hematology and Institute of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Chen X; Department of Hematology and Institute of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Pan X; Department of Hematology and Institute of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Deng X; Department of Hematology and Institute of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Li S; Department of Hematology and Institute of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Wang Z; Department of Hematology and Institute of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Wang J; Department of Hematology and Institute of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Liao D; Department of Hematology and Institute of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Xu J; Department of Hematology and Institute of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Chen M; Department of Hematology and Institute of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Zhao C; State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, China.
  • Xue Z; State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, China.
  • Wang Y; State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, China.
  • Niu T; Department of Hematology and Institute of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Lin J; State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, China.
  • Chen L; State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, China.
  • Liu Y; Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China.
  • Chen C; Department of Hematology and Institute of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
PLoS Biol ; 21(5): e3002088, 2023 05.
Article en En | MEDLINE | ID: mdl-37130348
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 Tmem134ß 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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Análisis de Expresión Génica de una Sola Célula Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Análisis de Expresión Génica de una Sola Célula Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos