BACKGROUND： The origin and classification of neural stem cells （NSCs） has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expressio...BACKGROUND： The origin and classification of neural stem cells （NSCs） has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease. To understand how one could manipulate NSC developmental programs for therapeutic use, additional work is needed to elucidate how NSCs are programmed and how signals during development are interpreted to determine cell fate. OBJECTIVE： This review describes the identification, classification and characterization of NSCs within the large neurogenic niche of the ventricular-subventricular zone （V-SVZ）. METHODS： A literature search was conducted using Pubmed including the keywords ＂ventricular-subventricular zone,＂ ＂neural stem cell,＂ ＂heterogeneity,＂ ＂identity＂ and/or ＂single cell＂ to find relevant manuscripts to include within the review. A special focus was placed on more recent findings using single-cell level analyses on neural stem cells within their niche（s）. RESULTS： This review discusses over 20 research articles detailing findings on V-SVZ NSC heterogeneity, over 25 articles describing fate determinants of NSCs, and focuses on 8 recent publications using distinct single-cell analyses of neural stem cells including fl0w cytometry and RNA-seq. Additionally, over 60 manuscripts highlighting the markers expressed on cells within the NSC lineage are included in a chart divided by cell type. CONCLUSIONS： Investigation of NSC heterogeneity and fate decisions is ongoing. Thus far, much research has been conducted in mice however, findings in human and other mammalian species are also discussed here. Implications of NSC heterogeneity established in the embryo for the properties of NSCs in the adult brain are explored, including how these cells may be redirected after injury or genetic manipulation.展开更多
目的观察丹龙醒脑方对脑缺血再灌注模型大鼠侧脑室室管膜下区(SVZ)神经干细胞(NSCs)增殖与Hes1、Hes5表达的影响,探讨其促进内源性NSCs增殖的作用机制。方法将80只雄性SD大鼠随机分为假手术组、模型组、依达拉奉组(依达组)、丹龙醒脑方...目的观察丹龙醒脑方对脑缺血再灌注模型大鼠侧脑室室管膜下区(SVZ)神经干细胞(NSCs)增殖与Hes1、Hes5表达的影响,探讨其促进内源性NSCs增殖的作用机制。方法将80只雄性SD大鼠随机分为假手术组、模型组、依达拉奉组(依达组)、丹龙醒脑方组(丹龙组)。采用线栓法制备局灶性脑缺血再灌注模型,再灌注7 d后取缺血侧SVZ脑组织。Brdu免疫荧光法检测SVZ NSCs增殖,RT-q PCR、Western blot分别检测Hes1、Hes5 m RNA和蛋白的表达。结果与假手术组比较,其余各组Brdu阳性细胞率增加,Hes1、Hes5 m RNA及蛋白表达明显升高(P<0.01);与模型组比较,依达组、丹龙组Brdu阳性细胞率明显增加,Hes1、Hes5 m RNA及蛋白表达水平明显增强(P<0.01);丹龙组Hes1 m RNA表达水平优于依达组(P<0.01),其余指标均无明显差异。结论丹龙醒脑方可促进脑缺血再灌注后大鼠SVZ NSCs增殖,并上调Hes1、Hes5表达水平,其机制可能与激活Notch信号通路有关。展开更多
We recently reported that targeted deletion of Pannexin 1 in neural precursor cells of the ventricular zone impairs the maintenance of these cells in healthy and stroke-injured brain. Here we frame this exciting new f...We recently reported that targeted deletion of Pannexin 1 in neural precursor cells of the ventricular zone impairs the maintenance of these cells in healthy and stroke-injured brain. Here we frame this exciting new finding in the context of our previous studies on Pannexin 1 in neural precursors as well as the close rela- tionship between Pannexin 1 and purinergic receptors established by other groups. Moreover, we identify important gaps in our understanding of Pannexin 1 in neural precursor cell biology in terms of the under- lying molecular mechanisms and functional/behavioural outcomes.展开更多
目的探讨体表心电图特点与右室流出道不同区域起搏的关系。方法入选186例行右室流出道起搏的患者,根据不同起搏位置,将患者分成间隔上部组(45例)、间隔下部组(24例)、前壁组(101例)及游离壁组(16例)。比较分析4组患者在右心室起搏状态...目的探讨体表心电图特点与右室流出道不同区域起搏的关系。方法入选186例行右室流出道起搏的患者,根据不同起搏位置,将患者分成间隔上部组(45例)、间隔下部组(24例)、前壁组(101例)及游离壁组(16例)。比较分析4组患者在右心室起搏状态下的体表心电图特点差异。结果 4组患者的临床一般资料比较,差异无统计学意义(P>0.05)。4组患者中,游离壁组QRS波时限为(173±14)ms,长于其他3组(P=0.014);QRS波群额面电轴间隔上部组为(61±47)°,而间隔下部组为(-18±52)°(P=0.01);间隔上部组胸前导联移行区指数(transitional zone Index,TZI)最小,而游离壁组最大(P=0.01);在4组患者肢体导联QRS主波方向比较中,间隔上部组下壁(Ⅱ,Ⅲ,a VF)导联QRS主波向上的比例最大。结论体表心电图特点有助于右室流出道起搏电极在不同区域的定位,但受样本量等的影响,仍需大样本的研究加以验证。展开更多
Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders(NDDs)that exhibit delayed speech development,intellectual disability,and congenital abnormalities.The etiology of NDDs i...Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders(NDDs)that exhibit delayed speech development,intellectual disability,and congenital abnormalities.The etiology of NDDs is unclear.Here we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells(RGCs),respectively,in the mouse neocortex during early gestation.Knockdown or dominant-negative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone(VZ).Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating VZ.The ectopic differentiation and deficient migration disappear when N-cadherin is over-expressed in RGCs.The data indicate that Foxp4 is essential for N-cadherin-based adherens junctions,the loss of which leads to periventricular heterotopias.We hypothesize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.展开更多
In this study, we investigated non-captive four-striped mice （Rhabdomys pumilio） for evidence that adult neurogenesis occurs in the adult brain of animal models in natural environment. Ki-67 （a marker for cell prol...In this study, we investigated non-captive four-striped mice （Rhabdomys pumilio） for evidence that adult neurogenesis occurs in the adult brain of animal models in natural environment. Ki-67 （a marker for cell proliferation） and doublecortin （a marker for immature neurons） immunos-taining conifrmed that adult neurogenesis occurs in the active sites of subventricular zone of the lateral ventricle with the migratory stream to the olfactory bulb, and the subgranular zone of the dentate gyrus of the hippocampus. No Ki-67 proliferating cells were observed in the striatum substantia nigra, amygdala, cerebral cortex or dorsal vagal complex. Doublecortin-immunore-active cells were observed in the striatum, third ventricle, cerebral cortex, amygdala, olfactory bulb and along the rostral migratory stream but absent in the substantia nigra and dorsal vagal complex. The potential neurogenic sites in the four-striped mouse species could invariably lead to increased neural plasticity.展开更多
文摘BACKGROUND： The origin and classification of neural stem cells （NSCs） has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease. To understand how one could manipulate NSC developmental programs for therapeutic use, additional work is needed to elucidate how NSCs are programmed and how signals during development are interpreted to determine cell fate. OBJECTIVE： This review describes the identification, classification and characterization of NSCs within the large neurogenic niche of the ventricular-subventricular zone （V-SVZ）. METHODS： A literature search was conducted using Pubmed including the keywords ＂ventricular-subventricular zone,＂ ＂neural stem cell,＂ ＂heterogeneity,＂ ＂identity＂ and/or ＂single cell＂ to find relevant manuscripts to include within the review. A special focus was placed on more recent findings using single-cell level analyses on neural stem cells within their niche（s）. RESULTS： This review discusses over 20 research articles detailing findings on V-SVZ NSC heterogeneity, over 25 articles describing fate determinants of NSCs, and focuses on 8 recent publications using distinct single-cell analyses of neural stem cells including fl0w cytometry and RNA-seq. Additionally, over 60 manuscripts highlighting the markers expressed on cells within the NSC lineage are included in a chart divided by cell type. CONCLUSIONS： Investigation of NSC heterogeneity and fate decisions is ongoing. Thus far, much research has been conducted in mice however, findings in human and other mammalian species are also discussed here. Implications of NSC heterogeneity established in the embryo for the properties of NSCs in the adult brain are explored, including how these cells may be redirected after injury or genetic manipulation.
文摘目的观察丹龙醒脑方对脑缺血再灌注模型大鼠侧脑室室管膜下区(SVZ)神经干细胞(NSCs)增殖与Hes1、Hes5表达的影响,探讨其促进内源性NSCs增殖的作用机制。方法将80只雄性SD大鼠随机分为假手术组、模型组、依达拉奉组(依达组)、丹龙醒脑方组(丹龙组)。采用线栓法制备局灶性脑缺血再灌注模型,再灌注7 d后取缺血侧SVZ脑组织。Brdu免疫荧光法检测SVZ NSCs增殖,RT-q PCR、Western blot分别检测Hes1、Hes5 m RNA和蛋白的表达。结果与假手术组比较,其余各组Brdu阳性细胞率增加,Hes1、Hes5 m RNA及蛋白表达明显升高(P<0.01);与模型组比较,依达组、丹龙组Brdu阳性细胞率明显增加,Hes1、Hes5 m RNA及蛋白表达水平明显增强(P<0.01);丹龙组Hes1 m RNA表达水平优于依达组(P<0.01),其余指标均无明显差异。结论丹龙醒脑方可促进脑缺血再灌注后大鼠SVZ NSCs增殖,并上调Hes1、Hes5表达水平,其机制可能与激活Notch信号通路有关。
基金Research in the Swayne lab was supported by operating grants to LAS from the Natural Sciences and Engineering Research Council of Canada(NSERC Discovery Grant)the Canadian Institutes of Health Research(CIHR Grant MOP142215)+5 种基金The Scottish Rite Charitable Foundation of Canada and the University of Victoria Division of Medical Sciencesby infrastructure grants from the Canadian Foundation for Innovation(CFI)the British Columbia Knowledge Development Fund(BCKDF)supported by a Michael Smith Foundation for Health Research and British Columbia Schizophrenia Society Foundation Scholar Awardsupported by a University of Victoria Fellowship Graduate Awardsupported by a Vanier Canada Graduate Scholarship(NSERC)
文摘We recently reported that targeted deletion of Pannexin 1 in neural precursor cells of the ventricular zone impairs the maintenance of these cells in healthy and stroke-injured brain. Here we frame this exciting new finding in the context of our previous studies on Pannexin 1 in neural precursors as well as the close rela- tionship between Pannexin 1 and purinergic receptors established by other groups. Moreover, we identify important gaps in our understanding of Pannexin 1 in neural precursor cell biology in terms of the under- lying molecular mechanisms and functional/behavioural outcomes.
文摘目的探讨体表心电图特点与右室流出道不同区域起搏的关系。方法入选186例行右室流出道起搏的患者,根据不同起搏位置,将患者分成间隔上部组(45例)、间隔下部组(24例)、前壁组(101例)及游离壁组(16例)。比较分析4组患者在右心室起搏状态下的体表心电图特点差异。结果 4组患者的临床一般资料比较,差异无统计学意义(P>0.05)。4组患者中,游离壁组QRS波时限为(173±14)ms,长于其他3组(P=0.014);QRS波群额面电轴间隔上部组为(61±47)°,而间隔下部组为(-18±52)°(P=0.01);间隔上部组胸前导联移行区指数(transitional zone Index,TZI)最小,而游离壁组最大(P=0.01);在4组患者肢体导联QRS主波方向比较中,间隔上部组下壁(Ⅱ,Ⅲ,a VF)导联QRS主波向上的比例最大。结论体表心电图特点有助于右室流出道起搏电极在不同区域的定位,但受样本量等的影响,仍需大样本的研究加以验证。
基金supported by the Wenzhou Municipal Science and Technology Bureau(Y20210901)the Natural Science Foundation of Zhejiang Province(LQ20H090001)the Scientific Research Fund of Wenling Science and Technology Bureau(2018C320001).
文摘Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders(NDDs)that exhibit delayed speech development,intellectual disability,and congenital abnormalities.The etiology of NDDs is unclear.Here we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells(RGCs),respectively,in the mouse neocortex during early gestation.Knockdown or dominant-negative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone(VZ).Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating VZ.The ectopic differentiation and deficient migration disappear when N-cadherin is over-expressed in RGCs.The data indicate that Foxp4 is essential for N-cadherin-based adherens junctions,the loss of which leads to periventricular heterotopias.We hypothesize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.
基金supported by Individual Faculty Research GrantSwiss-South Africa Joint Research Progamme(SSAJRP)
文摘In this study, we investigated non-captive four-striped mice （Rhabdomys pumilio） for evidence that adult neurogenesis occurs in the adult brain of animal models in natural environment. Ki-67 （a marker for cell proliferation） and doublecortin （a marker for immature neurons） immunos-taining conifrmed that adult neurogenesis occurs in the active sites of subventricular zone of the lateral ventricle with the migratory stream to the olfactory bulb, and the subgranular zone of the dentate gyrus of the hippocampus. No Ki-67 proliferating cells were observed in the striatum substantia nigra, amygdala, cerebral cortex or dorsal vagal complex. Doublecortin-immunore-active cells were observed in the striatum, third ventricle, cerebral cortex, amygdala, olfactory bulb and along the rostral migratory stream but absent in the substantia nigra and dorsal vagal complex. The potential neurogenic sites in the four-striped mouse species could invariably lead to increased neural plasticity.
