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Glioma stem cells and neural stem cells respond differently to BMP4 signaling

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摘要

© 2022, The Author(s).Malignant glioma is a highly heterogeneous and invasive primary brain tumor characterized by high recurrence rates, resistance to combined therapy, and dismal prognosis. Glioma stem cells (GSCs) are likely responsible for tumor progression, resistance to therapy, recurrence, and poor prognosis owing to their high self-renewal and tumorigenic potential. As a family member of BMP signaling, bone morphogenetic protein4 (BMP4) has been reported to induce the differentiation of GSCs and neural stem cells (NSCs). However, the molecular mechanisms underlying the BMP4-mediated effects in these two cell types are unclear. In this study, we treated hGSCs and hNSCs with BMP4 and compared the phenotypic and transcriptional changes between these two cell types. Phenotypically, we found that the growth of hGSCs was greatly inhibited by BMP4, but the same treatment only increased the cell size of hNSCs. While the RNA sequencing results showed that BMP4 treatment evoked significantly transcriptional changes in both hGSCs and hNSCs, the profiles of differentially expressed genes were distinct between the two groups. A gene set that specifically targeted the proliferation and differentiation of hGSCs but not hNSCs was enriched and then validated in hGSC culture. Our results suggested that hGSCs and hNSCs responded differently to BMP4 stimulation. Understanding and investigating different responses between hGSCs and hNSCs will benefit finding partner factors working together with BMP4 to further suppress GSCs proliferation and stemness without disturbing NSCs.

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  • 来源
    《cell regeneration》 |2022年第1期|共页
  • 作者

    Han X.-X.; Cai C.; Yu L.-M.Wang M.Yang W.Hu D.-Y.Ren J.Zhu L.-Y.Deng J.-J.Chen Q.-Q.He H.Gao Z.;

  • 作者单位

    Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases Shanghai Stomatological Hospital & School of Stomatology Fudan University;

    Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center) Tongji University School of Medicine;

    Institute of Geriatrics (Shanghai University) Affiliated Nantong Hospital of Shanghai University (The Sixth People’s Hospital of Nantong) School of Medicine Shanghai UniversitySchool of Medicine Jiaxing UniversityDepartment of Neurosurgery Changzheng Hospital Second Military Medical UniversityDepartment of Neurosurgery Third Affiliated Hospital of Second Military Medical University;

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  • 正文语种 英语
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  • 关键词

    BMP4; Cell differentiation; Cell proliferation; Glioma stem cells; Neural stem cells;

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