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Single-cell transcriptome reveals cellular hierarchies and guides p-EMT-targeted trial in skull base chordoma.
Zhang, Qilin; Fei, Lijiang; Han, Rui; Huang, Ruofan; Wang, Yongfei; Chen, Hong; Yao, Boyuan; Qiao, Nidan; Wang, Zhe; Ma, Zengyi; Ye, Zhao; Zhang, Yichao; Wang, Weiwei; Wang, Ye; Kong, Lin; Shou, Xuefei; Cao, Xiaoyun; Zhou, Xiang; Shen, Ming; Cheng, Haixia; Yao, Zhenwei; Zhang, Chao; Guo, Guoji; Zhao, Yao.
Afiliación
  • Zhang Q; Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Fei L; National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Han R; Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • Huang R; Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Wang Y; National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Chen H; National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Yao B; Department of Oncology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Qiao N; Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Wang Z; National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Ma Z; National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Ye Z; Department of Pathology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Zhang Y; Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Wang W; National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Wang Y; Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Kong L; National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Shou X; Department of Plastic and Reconstructive Surgery, Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Cao X; Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Zhou X; National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Shen M; Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Cheng H; National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Yao Z; Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Zhang C; National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Guo G; National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Zhao Y; Department of Radiology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Cell Discov ; 8(1): 94, 2022 Sep 20.
Article en En | MEDLINE | ID: mdl-36127333
Skull base chordoma (SBC) is a bone cancer with a high recurrence rate, high radioresistance rate, and poorly understood mechanism. Here, we profiled the transcriptomes of 90,691 single cells, revealed the SBC cellular hierarchies, and explored novel treatment targets. We identified a cluster of stem-like SBC cells that tended to be distributed in the inferior part of the tumor. Combining radiated UM-Chor1 RNA-seq data and in vitro validation, we further found that this stem-like cell cluster is marked by cathepsin L (CTSL), a gene involved in the packaging of telomere ends, and may be responsible for radioresistance. Moreover, signatures related to partial epithelial-mesenchymal transition (p-EMT) were found to be significant in malignant cells and were related to the invasion and poor prognosis of SBC. Furthermore, YL-13027, a p-EMT inhibitor that acts through the TGF-ß signaling pathway, demonstrated remarkable potency in inhibiting the invasiveness of SBC in preclinical models and was subsequently applied in a phase I clinical trial that enrolled three SBC patients. Encouragingly, YL-13027 attenuated the growth of SBC and achieved stable disease with no serious adverse events, underscoring the clinical potential for the precision treatment of SBC with this therapy. In summary, we conducted the first single-cell RNA sequencing of SBC and identified several targets that could be translated to the treatment of SBC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Discov Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Discov Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido