目的检测脑胶质瘤肿瘤组织和外周血中homeodomain only protein X(HOPX)基因甲基化状态并探讨其临床意义。方法选取病理证实为脑胶质瘤患者的胶质瘤组织及其外周血血浆标本共52例为实验组,选取因颅脑外伤患者术中弃除的坏死脑组织及其...目的检测脑胶质瘤肿瘤组织和外周血中homeodomain only protein X(HOPX)基因甲基化状态并探讨其临床意义。方法选取病理证实为脑胶质瘤患者的胶质瘤组织及其外周血血浆标本共52例为实验组,选取因颅脑外伤患者术中弃除的坏死脑组织及其外周血血浆标本共20例为对照组,采用甲基化特异性聚合酶链反应和亚硫酸氢盐测序PCR法检测实验组及对照组HOPX基因甲基化状态。结果实验组脑胶质瘤组织和对照组坏死脑组织中HOPX基因甲基化率分别为71.15%(37/52)和20.0%(4/20),实验组脑胶质瘤患者外周血血浆和对照组颅脑外伤患者外周血血浆中HOPX基因甲基化率分别为65.38%(34/52)和15.0%(3/20),脑胶质瘤患者肿瘤组织及外周血中HOPX基因甲基化率与患者性别、年龄、病理类型、肿瘤部位、病理分级间无明显相关性。结论脑胶质瘤患者肿瘤组织和外周血血浆中HOPX基因甲基化率较高,可能与脑胶质瘤的发生相关,因其检测灵敏度较高,有望为脑胶质瘤患者提供早期诊断的线索和依据,为脑胶质瘤的治疗提供新的思路。展开更多
Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interne...Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interneurons. One of prominent features of the human cortex is enriched with glial cells, but there are major gaps in understanding how these glial cells are generated. Herein, by integrating analysis of published human cortical single-cell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFR-expressing human cortical truncated radial glial cells (tRGs) give rise to basal multipotent intermediate progenitors (bMIPCs) that express EGFR, ASCL1, OLIG2 and OLIG1. These bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocytes, astrocytes and olfactory bulb interneurons. We also characterized molecular features of the cortical tRG. Integration of our findings suggests a general picture of the lineage progression of cortical radial glial cells, a fundamental process of the developing human cerebral cortex.展开更多
文摘目的检测脑胶质瘤肿瘤组织和外周血中homeodomain only protein X(HOPX)基因甲基化状态并探讨其临床意义。方法选取病理证实为脑胶质瘤患者的胶质瘤组织及其外周血血浆标本共52例为实验组,选取因颅脑外伤患者术中弃除的坏死脑组织及其外周血血浆标本共20例为对照组,采用甲基化特异性聚合酶链反应和亚硫酸氢盐测序PCR法检测实验组及对照组HOPX基因甲基化状态。结果实验组脑胶质瘤组织和对照组坏死脑组织中HOPX基因甲基化率分别为71.15%(37/52)和20.0%(4/20),实验组脑胶质瘤患者外周血血浆和对照组颅脑外伤患者外周血血浆中HOPX基因甲基化率分别为65.38%(34/52)和15.0%(3/20),脑胶质瘤患者肿瘤组织及外周血中HOPX基因甲基化率与患者性别、年龄、病理类型、肿瘤部位、病理分级间无明显相关性。结论脑胶质瘤患者肿瘤组织和外周血血浆中HOPX基因甲基化率较高,可能与脑胶质瘤的发生相关,因其检测灵敏度较高,有望为脑胶质瘤患者提供早期诊断的线索和依据,为脑胶质瘤的治疗提供新的思路。
基金This work was supported by grants from National Key Research and Development Program of China(2018YFA0108000)National Natural Science Foundation of China(31820103006,31630032,and 32070971)+1 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,and Shanghai Center for Brain Science and Brain-Inspired Technology.We thank Dr.John L.Rubenstein for critical reading of the manuscript.
文摘Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interneurons. One of prominent features of the human cortex is enriched with glial cells, but there are major gaps in understanding how these glial cells are generated. Herein, by integrating analysis of published human cortical single-cell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFR-expressing human cortical truncated radial glial cells (tRGs) give rise to basal multipotent intermediate progenitors (bMIPCs) that express EGFR, ASCL1, OLIG2 and OLIG1. These bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocytes, astrocytes and olfactory bulb interneurons. We also characterized molecular features of the cortical tRG. Integration of our findings suggests a general picture of the lineage progression of cortical radial glial cells, a fundamental process of the developing human cerebral cortex.
