The presence or absence of adult neural stem cells in the mammalian forebrain ependyma has been debated for two decades.In this study,we performed single-cell RNA sequencing to investigate the cellular composition of ...The presence or absence of adult neural stem cells in the mammalian forebrain ependyma has been debated for two decades.In this study,we performed single-cell RNA sequencing to investigate the cellular composition of the ependymal surface of the adult mouse forebrain using whole mounts of lateral walls of lateral ventricles.We identified 12 different cell subtypes in the ependymal surface.Immunocytochemical analyses revealed that CD133^(+)multi-ciliated cells comprised 67.6%of ependymal cells,while the remaining 32.4%were CD133^(-).CD133^(+)ependymal cells can be further classified into FOXJ1^(+)/SOX2^(+)/ACTA2^(+)cells,FLT1^(+)/CD31^(+)/CLDN5^(+)endothelial-like cells,and PDGFRB^(+)/VTN^(+)/NG2^(+)pericyte-like cells,as well as endothelial-pericyte-like cells and Foxj1^(+)endothelial-like cells.CD133^(-)ependymal cells can be further divided into endothelial-like cells,Foxj1^(+)ependymal cells,Foxj1^(+)endothelial-like cells,pericyte-like cells,endothelial-pericyte-like cells,VIM^(+)cells,and cells negative for all of these markers.This comprehensive profiling confirms the heterogeneity of the ependymal surface in the adult mouse forebrain.Debate regarding whether adult ependymal cells contain neural stem cells has arisen because different researchers have examined different populations of ependymal cells.Our study provides a new perspective for investigation of clinical endogenous neural stem cells,ultimately paving the way for stem cell therapies in neurological diseases.展开更多
目的探究超高海拔驻防军人情绪调节策略的群体特征及其在心理应激与睡眠障碍间的中介机制。方法采用横断面研究设计,于2024年12月至2025年4月在四川省甘孜藏族自治州(海拔3980~4200 m)的部队以便利抽样法纳入401名驻防军人。使用军人心...目的探究超高海拔驻防军人情绪调节策略的群体特征及其在心理应激与睡眠障碍间的中介机制。方法采用横断面研究设计,于2024年12月至2025年4月在四川省甘孜藏族自治州(海拔3980~4200 m)的部队以便利抽样法纳入401名驻防军人。使用军人心理应激自评问卷(psychological stress self-evaluation test for military personnel,PSET)、情绪调节问卷(emotion regulation questionnaire,ERQ)和匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)进行测评。采用结构方程模型检验情绪调节策略在心理应激与睡眠障碍之间的中介效应。结果超高海拔军人睡眠障碍发生率为20.2%,其中轻度睡眠障碍发生率为18.45%。睡眠障碍总分与表达抑制(r=0.23)、心理应激(r=0.53)呈显著正相关(P<0.01)。表达抑制在心理应激与睡眠障碍间起部分正向中介作用,中介效应占总效应的3.63%。结论超高海拔驻防军人情绪调节策略的使用频率随心理应激水平升高而增加;建议针对高应激群体开展替代表达抑制策略的心理训练,以改善其睡眠质量。展开更多
The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitte...The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.展开更多
Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that pla...Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that plays an important role in a broad range of cellular activities from calcium regulation to protein synthesis and trafficking.In neurons,the ER extends from the soma through the axon to presynaptic terminals,and throughout the dendritic arbor into as many as half of all postsynaptic dendritic spines at any given time(Falahati et al.,2022).展开更多
Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although th...Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although the CNCC migration has been well-studied,the role of the niche in relation to CNCC remains unclear.Variants in FOXI3 have been implicated in craniofacial microsomia(CFM),yet the molecular mechanisms remain unexplored.FOXI3 is expressed in the ectoderm and auricle epidermis,but not in CNCCs or cartilage.Deletion of Foxi3 in the mouse CNCCs did not disrupt mandible and auricular development,further confirming that FOXI3 does not directly regulate CNCCs.However,Foxi3 deficiency in the ectoderm reduced the production of chondrogenesis-related cytokines derived from ectodermal cells,such as TGF-β1.This impairment affected CNCC proliferation through cell communication,subsequently altering the development of the mandible and auricle.These results emphasize the critical role of FOXI3 in establishing the microenvironment supporting CNCC function.Furthermore,FOXI3 directly regulates target genes associated with translation,thereby orchestrating cytokine production in epidermal cells.The validation using auricle sample from a CFM patient carrying FOXI3 mutation further supports our findings.These insights highlight the function of FOXI3 in creating the niche necessary for CNCC development and provide a basis for understanding the molecular mechanisms driving CFM pathogenesis.展开更多
Progranulin(PGRN),encoded by the GRN gene,is a secreted glycoprotein that undergoes proteolytic cleavage to generate individual granulin peptides(granulin A-G)capable of exerting distinct biological functions.PGRN is ...Progranulin(PGRN),encoded by the GRN gene,is a secreted glycoprotein that undergoes proteolytic cleavage to generate individual granulin peptides(granulin A-G)capable of exerting distinct biological functions.PGRN is widely expressed in multiple tissues,including the central nervous and immune systems.Within the central nervous system,PGRN is highly expressed in the hippocampus,cerebral cortex,and hypothalamus,and has been detected in various neuronal subtypes,including Purkinje cells and motor neurons,where it plays a crucial role in neuronal functions,such as neurite outgrowth and synaptic plasticity.In addition to neurons,PGRN is expressed in glial cells,particularly in microglia,where it regulates phagocytosis.Furthermore,PGRN is presented in peripheral immune cells,including macrophages,and contributes to the regulation of inflammatory responses.PGRN exerts its diverse functions via binding partners,including receptors such as sortilin,EphA2,Notch,death receptor 3,and toll-like receptor 9(Chitramuthu et al.,2017).展开更多
The adult subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal dentate gyrus(DG)are the two brain regions where neurogenesis occurs throughout life in the adult mammalian brain(Min...The adult subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal dentate gyrus(DG)are the two brain regions where neurogenesis occurs throughout life in the adult mammalian brain(Ming and Song,2011).Adult quiescent hippocampal neural stem cells(NSCs)are bona fide stem cells and,when activated,give rise to newborn granule neurons in the adult brain,which play vital roles in learning,memory,mood,and affective cognition(Bonaguidi et al.,2011;Ming and Song,2011).展开更多
Growing evidence suggests that exercise can provide neuroprotection by improving mitochondrial quality control(MQC)on the aged brain.Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)signaling responsiven...Growing evidence suggests that exercise can provide neuroprotection by improving mitochondrial quality control(MQC)on the aged brain.Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)signaling responsiveness declines with aging.However,whether AMPK plays a role in the exercise-mediated improvement of memory and MQC in the aged hippocampus remains to be established.5-Aminoimidazole 4-carboxamide ribonucleoside(AICAR),a pharmacological agonist of AMPK,has been proposed to be an exercise mimetic recently.However,it has not been clarified whether AICAR could mimic the effects of exercise on the aged hippocampus through improvement of MQC.In this study,AICAR(AMPK agonist)and Compound C(AMPK inhibitor)were used to investigate if AMPK plays a key role in exercise-induced improvement of MQC and if AICAR could act as an exercise mimetic through improvement of MQC in aged hippocampus.Both exercise and AICAR improved the memory of aged mice and increased AMPK phosphorylation in the aged hippocampus.Exercise,but not AICAR,improved mitochondrial respiratory function in the aged hippocampus and increased the microtubule associated protein 1 light chain 3(LC3)-II/LC3-I ratio and the protein expression of LC3-II and autophagy related protein 7(ATG7)in the lysate of whole hippocampal tissue.Both exercise and AICAR increased the ratio of LC3-II/LC3-I and the protein expression of LC3-II in the mitochondrial fractions of the hippocampus.Regarding mitochondrial dynamics,neither exercise training nor AICAR changed the protein level of mitofusin 2(Mfn2).Exercise,but not AICAR,increased the protein level of dynamin-related protein 1(Drp1).Furthermore,both exercise training and AICAR increased the protein level of peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α),a modulator of mitochondrial biogenesis.Compound C abolished the exercise-induced effects on memory in aged mice,AMPK phosphorylation,autophagy,mitophagy,and mitochondrial fission in the aged hippocampus.However,Compound C did not reverse the exercise-induced increase in PGC-1α protein levels in the aged hippocampus.Our data provide evidence that AMPK plays an important role in the exercise-induced improvement of memory and MQC in the hippocampus of aged mice.Importantly,we demonstrated for the first time that AICAR could partially mimetic the beneficial effects of endurance exercise on memory and MQC in the hippocampus of aged mice,and thus may be a promising exercise mimetic for counteracting brain aging.展开更多
Lymphatic vessel networks have been identified in the meninges of mice,non-human primates,and humans[1].Meningeal lymphatic vessels(mLVs),composed of meningeal lymphatic endothelial cells(mLECs),are present in both ze...Lymphatic vessel networks have been identified in the meninges of mice,non-human primates,and humans[1].Meningeal lymphatic vessels(mLVs),composed of meningeal lymphatic endothelial cells(mLECs),are present in both zebrafish and mammals,although their anatomical distributions differ;they reside in the dura mater in mice,but are situated within the meninges in zebrafish[2].Moreover,the lymphatic marker genes expressed in these vessels differ between species[2].展开更多
The number and diversity of inhibitory neurons(INs)increased substantially during mammalian brain evolution.However,the generative mechanisms of the vast repertoire of human INs remain elusive.We performed spatial and...The number and diversity of inhibitory neurons(INs)increased substantially during mammalian brain evolution.However,the generative mechanisms of the vast repertoire of human INs remain elusive.We performed spatial and single-cell transcriptomics of human medial ganglionic eminence(hMGE),a pivotal source of cortical and subpallial INs,and built the trajectories of hMGE-derived cells during brain development.We identified spatiotemporally and molecularly segregated progenitor cell populations fated to produce distinct IN types.展开更多
基金supported by the State Key Program of the National Natural Science Foundation of China,No.82030035(to YES)Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai(to LZ).
文摘The presence or absence of adult neural stem cells in the mammalian forebrain ependyma has been debated for two decades.In this study,we performed single-cell RNA sequencing to investigate the cellular composition of the ependymal surface of the adult mouse forebrain using whole mounts of lateral walls of lateral ventricles.We identified 12 different cell subtypes in the ependymal surface.Immunocytochemical analyses revealed that CD133^(+)multi-ciliated cells comprised 67.6%of ependymal cells,while the remaining 32.4%were CD133^(-).CD133^(+)ependymal cells can be further classified into FOXJ1^(+)/SOX2^(+)/ACTA2^(+)cells,FLT1^(+)/CD31^(+)/CLDN5^(+)endothelial-like cells,and PDGFRB^(+)/VTN^(+)/NG2^(+)pericyte-like cells,as well as endothelial-pericyte-like cells and Foxj1^(+)endothelial-like cells.CD133^(-)ependymal cells can be further divided into endothelial-like cells,Foxj1^(+)ependymal cells,Foxj1^(+)endothelial-like cells,pericyte-like cells,endothelial-pericyte-like cells,VIM^(+)cells,and cells negative for all of these markers.This comprehensive profiling confirms the heterogeneity of the ependymal surface in the adult mouse forebrain.Debate regarding whether adult ependymal cells contain neural stem cells has arisen because different researchers have examined different populations of ependymal cells.Our study provides a new perspective for investigation of clinical endogenous neural stem cells,ultimately paving the way for stem cell therapies in neurological diseases.
文摘目的探究超高海拔驻防军人情绪调节策略的群体特征及其在心理应激与睡眠障碍间的中介机制。方法采用横断面研究设计,于2024年12月至2025年4月在四川省甘孜藏族自治州(海拔3980~4200 m)的部队以便利抽样法纳入401名驻防军人。使用军人心理应激自评问卷(psychological stress self-evaluation test for military personnel,PSET)、情绪调节问卷(emotion regulation questionnaire,ERQ)和匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)进行测评。采用结构方程模型检验情绪调节策略在心理应激与睡眠障碍之间的中介效应。结果超高海拔军人睡眠障碍发生率为20.2%,其中轻度睡眠障碍发生率为18.45%。睡眠障碍总分与表达抑制(r=0.23)、心理应激(r=0.53)呈显著正相关(P<0.01)。表达抑制在心理应激与睡眠障碍间起部分正向中介作用,中介效应占总效应的3.63%。结论超高海拔驻防军人情绪调节策略的使用频率随心理应激水平升高而增加;建议针对高应激群体开展替代表达抑制策略的心理训练,以改善其睡眠质量。
基金supported by the Center for Cognition and Sociality,Institute for Basic Science(IBS)(IBS-R001-D2)(to WK).
文摘The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.
基金supported by AHA Career Development Award 938683 (to PJD)NIH grant R01MH123700 (to MLD)
文摘Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that plays an important role in a broad range of cellular activities from calcium regulation to protein synthesis and trafficking.In neurons,the ER extends from the soma through the axon to presynaptic terminals,and throughout the dendritic arbor into as many as half of all postsynaptic dendritic spines at any given time(Falahati et al.,2022).
基金supported by the National Natural Science Foundation of China(No.82271889,82572117,82371173,82172105)the National Key Research and Development Program of China(No.2021YFC2701000)Shanghai Natural Science Foundation(23ZR1409400,24ZR1409400)。
文摘Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although the CNCC migration has been well-studied,the role of the niche in relation to CNCC remains unclear.Variants in FOXI3 have been implicated in craniofacial microsomia(CFM),yet the molecular mechanisms remain unexplored.FOXI3 is expressed in the ectoderm and auricle epidermis,but not in CNCCs or cartilage.Deletion of Foxi3 in the mouse CNCCs did not disrupt mandible and auricular development,further confirming that FOXI3 does not directly regulate CNCCs.However,Foxi3 deficiency in the ectoderm reduced the production of chondrogenesis-related cytokines derived from ectodermal cells,such as TGF-β1.This impairment affected CNCC proliferation through cell communication,subsequently altering the development of the mandible and auricle.These results emphasize the critical role of FOXI3 in establishing the microenvironment supporting CNCC function.Furthermore,FOXI3 directly regulates target genes associated with translation,thereby orchestrating cytokine production in epidermal cells.The validation using auricle sample from a CFM patient carrying FOXI3 mutation further supports our findings.These insights highlight the function of FOXI3 in creating the niche necessary for CNCC development and provide a basis for understanding the molecular mechanisms driving CFM pathogenesis.
基金SENSHIN Medical Research Foundation,Takeda Science Foundation,Taiju Life Social Welfare Foundation,Mitsui Sumitomo Insurance Welfare Foundation,Research Foundation for Pharmaceutical Sciences,Tokyo Medical University Research Grant,JSPS KAKENHI(23K06369)to SKJSPS KAKENHI(24K02187)to KK.
文摘Progranulin(PGRN),encoded by the GRN gene,is a secreted glycoprotein that undergoes proteolytic cleavage to generate individual granulin peptides(granulin A-G)capable of exerting distinct biological functions.PGRN is widely expressed in multiple tissues,including the central nervous and immune systems.Within the central nervous system,PGRN is highly expressed in the hippocampus,cerebral cortex,and hypothalamus,and has been detected in various neuronal subtypes,including Purkinje cells and motor neurons,where it plays a crucial role in neuronal functions,such as neurite outgrowth and synaptic plasticity.In addition to neurons,PGRN is expressed in glial cells,particularly in microglia,where it regulates phagocytosis.Furthermore,PGRN is presented in peripheral immune cells,including macrophages,and contributes to the regulation of inflammatory responses.PGRN exerts its diverse functions via binding partners,including receptors such as sortilin,EphA2,Notch,death receptor 3,and toll-like receptor 9(Chitramuthu et al.,2017).
基金supported by National Institutes of Health(R35NS137480,R35NS116843,and RF1AG079557)by Dr.Miriam and Sheldon G.Adelson Medical Research Foundation.
文摘The adult subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal dentate gyrus(DG)are the two brain regions where neurogenesis occurs throughout life in the adult mammalian brain(Ming and Song,2011).Adult quiescent hippocampal neural stem cells(NSCs)are bona fide stem cells and,when activated,give rise to newborn granule neurons in the adult brain,which play vital roles in learning,memory,mood,and affective cognition(Bonaguidi et al.,2011;Ming and Song,2011).
基金supported by grants from the National Natural Science Foundation of China(81301128,81771500,82202789,82205065)the 2022 Suzhou Health Youth Backbone Talent“National Tutorial System”Training Project(Qngg2022024)+2 种基金the Science and Technology Project of Suzhou City of China(SKJYD2021195)the Science,Technology and Innovation Commission of Shenzhen(JCYJ20220530165211026)the Postgraduate Research and Practice Innovation Program in Jiangsu Province(KYCX22_3157,KYCX24_3371,YCX25_3517).
文摘Growing evidence suggests that exercise can provide neuroprotection by improving mitochondrial quality control(MQC)on the aged brain.Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)signaling responsiveness declines with aging.However,whether AMPK plays a role in the exercise-mediated improvement of memory and MQC in the aged hippocampus remains to be established.5-Aminoimidazole 4-carboxamide ribonucleoside(AICAR),a pharmacological agonist of AMPK,has been proposed to be an exercise mimetic recently.However,it has not been clarified whether AICAR could mimic the effects of exercise on the aged hippocampus through improvement of MQC.In this study,AICAR(AMPK agonist)and Compound C(AMPK inhibitor)were used to investigate if AMPK plays a key role in exercise-induced improvement of MQC and if AICAR could act as an exercise mimetic through improvement of MQC in aged hippocampus.Both exercise and AICAR improved the memory of aged mice and increased AMPK phosphorylation in the aged hippocampus.Exercise,but not AICAR,improved mitochondrial respiratory function in the aged hippocampus and increased the microtubule associated protein 1 light chain 3(LC3)-II/LC3-I ratio and the protein expression of LC3-II and autophagy related protein 7(ATG7)in the lysate of whole hippocampal tissue.Both exercise and AICAR increased the ratio of LC3-II/LC3-I and the protein expression of LC3-II in the mitochondrial fractions of the hippocampus.Regarding mitochondrial dynamics,neither exercise training nor AICAR changed the protein level of mitofusin 2(Mfn2).Exercise,but not AICAR,increased the protein level of dynamin-related protein 1(Drp1).Furthermore,both exercise training and AICAR increased the protein level of peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α),a modulator of mitochondrial biogenesis.Compound C abolished the exercise-induced effects on memory in aged mice,AMPK phosphorylation,autophagy,mitophagy,and mitochondrial fission in the aged hippocampus.However,Compound C did not reverse the exercise-induced increase in PGC-1α protein levels in the aged hippocampus.Our data provide evidence that AMPK plays an important role in the exercise-induced improvement of memory and MQC in the hippocampus of aged mice.Importantly,we demonstrated for the first time that AICAR could partially mimetic the beneficial effects of endurance exercise on memory and MQC in the hippocampus of aged mice,and thus may be a promising exercise mimetic for counteracting brain aging.
基金supported by the National Natural Science Foundation of China(32220103006 and 82271524).
文摘Lymphatic vessel networks have been identified in the meninges of mice,non-human primates,and humans[1].Meningeal lymphatic vessels(mLVs),composed of meningeal lymphatic endothelial cells(mLECs),are present in both zebrafish and mammals,although their anatomical distributions differ;they reside in the dura mater in mice,but are situated within the meninges in zebrafish[2].Moreover,the lymphatic marker genes expressed in these vessels differ between species[2].
文摘The number and diversity of inhibitory neurons(INs)increased substantially during mammalian brain evolution.However,the generative mechanisms of the vast repertoire of human INs remain elusive.We performed spatial and single-cell transcriptomics of human medial ganglionic eminence(hMGE),a pivotal source of cortical and subpallial INs,and built the trajectories of hMGE-derived cells during brain development.We identified spatiotemporally and molecularly segregated progenitor cell populations fated to produce distinct IN types.
