The adult cortex has long been regarded as non-neurogenic.Whether injury can induce neurogenesis in the adult cortex is still controversial.Here,we report that focal ischemia stimulates a transient wave of local neuro...The adult cortex has long been regarded as non-neurogenic.Whether injury can induce neurogenesis in the adult cortex is still controversial.Here,we report that focal ischemia stimulates a transient wave of local neurogenesis.Using 5′-bromo-2′-deoxyuridine labeling,we demonstrated a rapid generation of doublecortin-positive neuroblasts that died quickly in mouse cerebral cortex following ischemia.Nestin-Cre^(ER)-based cell ablation and fate mapping showed a small contribution of neuroblasts by subventricular zone neural stem cells.Using a mini-photothrombotic ischemia mouse model and retrovirus expressing green fluorescent protein labeling,we observed maturation of locally generated new neurons.Furthermore,fate tracing analyses using PDGFRα-,GFAP-,and Sox2-Cre^(ER) mice showed a transient wave of neuroblast generation in mild ischemic cortex and identified that Sox2-positive astrocytes were the major neurogenic cells in adult cortex.In addition,a similar upregulation of Sox2 and appearance of neuroblasts were observed in the focal ischemic cortex of Macaca mulatta.Our findings demonstrated a transient neurogenic response of Sox2-positive astrocytes in ischemic cortex,which suggests the possibility of inducing neuronal regeneration by amplifying this intrinsic response in the future.展开更多
Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is ur...Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC.Here,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients.We found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)group.The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ESCC.Additionally,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells.Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback.Therefore,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.展开更多
目的研究肿瘤干细胞标记物CD133、CD44、SOX2、OCT4、ALDH1在非小细胞肺癌(NSCLC)组织中的表达及临床意义,为探索非小细胞肺癌肿瘤干细胞提供参考。方法采用免疫组织化学方法检测70例NSCLC组织、14例非癌组织中的CD133、CD44、SOX2、OCT...目的研究肿瘤干细胞标记物CD133、CD44、SOX2、OCT4、ALDH1在非小细胞肺癌(NSCLC)组织中的表达及临床意义,为探索非小细胞肺癌肿瘤干细胞提供参考。方法采用免疫组织化学方法检测70例NSCLC组织、14例非癌组织中的CD133、CD44、SOX2、OCT4、ALDH1蛋白的表达并对结果进行分析。结果 (1)CD133、CD44、SOX2、OCT4、ALDH1在70例NSCLC组织中的阳性表达率分别为88.57%、98.57%、100%、100%、100%,强阳性表达率分别为48.57%、67.14%、67.14%、31.43%、50%;CD133、C C D 4 4在N S C L C与非癌组织中的表达差异存在统计学意义(P均<0.0001),SOX2、OCT4、ALDH1在NSCLC与非癌组织中的表达差异无统计学意义(P均>0.05)。(2)随着病理级别的升高,CD133、CD44、SOX2、OCT4及ALDH1的表达呈上升趋势,分化越低的NSCLC表达上述指标的概率越高,其中CD133、SOX2、OCT4的表达在高、中、低分化组织中差异存在统计学意义(P值分别为0.001、0.040、<0.0001);CD133的表达在吸烟史、分化程度、淋巴结转移、肿瘤分期四个因素上差异存在统计学意义(P值分别为0.033、0.001、0.033、0.046);CD44与SOX2的表达在年龄上的差异存在统计学意义(P值分别为0.001、0.040)。结论 NSCLC组织中CD133、CD44、SOX2、OCT4、ALDH1阳性率高,CD133、CD44的表达明显高于非癌组织;CD133、SOX2、OCT4与NSCLC的恶性程度有关;CD44与SOX2与年龄因素有关。展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171346(to YZW)82171269(to JLY)+1 种基金82171471(to HF)Beijing Nova Program,No.Z201100006820076(to JLY).
文摘The adult cortex has long been regarded as non-neurogenic.Whether injury can induce neurogenesis in the adult cortex is still controversial.Here,we report that focal ischemia stimulates a transient wave of local neurogenesis.Using 5′-bromo-2′-deoxyuridine labeling,we demonstrated a rapid generation of doublecortin-positive neuroblasts that died quickly in mouse cerebral cortex following ischemia.Nestin-Cre^(ER)-based cell ablation and fate mapping showed a small contribution of neuroblasts by subventricular zone neural stem cells.Using a mini-photothrombotic ischemia mouse model and retrovirus expressing green fluorescent protein labeling,we observed maturation of locally generated new neurons.Furthermore,fate tracing analyses using PDGFRα-,GFAP-,and Sox2-Cre^(ER) mice showed a transient wave of neuroblast generation in mild ischemic cortex and identified that Sox2-positive astrocytes were the major neurogenic cells in adult cortex.In addition,a similar upregulation of Sox2 and appearance of neuroblasts were observed in the focal ischemic cortex of Macaca mulatta.Our findings demonstrated a transient neurogenic response of Sox2-positive astrocytes in ischemic cortex,which suggests the possibility of inducing neuronal regeneration by amplifying this intrinsic response in the future.
基金funded by the Department of Education of Yunnan Province(No.2021J0244).
文摘Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC.Here,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients.We found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)group.The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ESCC.Additionally,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells.Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback.Therefore,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.
文摘目的研究肿瘤干细胞标记物CD133、CD44、SOX2、OCT4、ALDH1在非小细胞肺癌(NSCLC)组织中的表达及临床意义,为探索非小细胞肺癌肿瘤干细胞提供参考。方法采用免疫组织化学方法检测70例NSCLC组织、14例非癌组织中的CD133、CD44、SOX2、OCT4、ALDH1蛋白的表达并对结果进行分析。结果 (1)CD133、CD44、SOX2、OCT4、ALDH1在70例NSCLC组织中的阳性表达率分别为88.57%、98.57%、100%、100%、100%,强阳性表达率分别为48.57%、67.14%、67.14%、31.43%、50%;CD133、C C D 4 4在N S C L C与非癌组织中的表达差异存在统计学意义(P均<0.0001),SOX2、OCT4、ALDH1在NSCLC与非癌组织中的表达差异无统计学意义(P均>0.05)。(2)随着病理级别的升高,CD133、CD44、SOX2、OCT4及ALDH1的表达呈上升趋势,分化越低的NSCLC表达上述指标的概率越高,其中CD133、SOX2、OCT4的表达在高、中、低分化组织中差异存在统计学意义(P值分别为0.001、0.040、<0.0001);CD133的表达在吸烟史、分化程度、淋巴结转移、肿瘤分期四个因素上差异存在统计学意义(P值分别为0.033、0.001、0.033、0.046);CD44与SOX2的表达在年龄上的差异存在统计学意义(P值分别为0.001、0.040)。结论 NSCLC组织中CD133、CD44、SOX2、OCT4、ALDH1阳性率高,CD133、CD44的表达明显高于非癌组织;CD133、SOX2、OCT4与NSCLC的恶性程度有关;CD44与SOX2与年龄因素有关。
