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Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory

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Neural Regeneration Research 2024年第5期19卷 1133-1141页

作者： Baicheng Zhao Hang Zhang Ying Liu Gaoyu Zu Yuxiao Zhang Jiayi Hu Shuai Liu linya you Department of Human Anatomy&Histoembryology School of Basic Medical SciencesFudan UniversityShanghaiChina Shanghai Key Laboratory of Brain Functional Genomics(Ministry of Education) Affiliated Mental Health Center(ECNU)School of Psychology and Cognitive ScienceEast China Normal UniversityShanghaiChina Shanghai Changning Mental Health Center ShanghaiChina NYU-ECNU Institute of Brain and Cognitive Science at NYU Shanghai ShanghaiChina Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai ShanghaiChina

Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/***1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual *** previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and ***,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory *** test this,we knocked out Brpf1 in forebrain excitatory neurons using *** found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in *** findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.

关键词： behavioral test Brpf1 CAMKIIa-Cre intellectual disability miniature excitatory postsynaptic current mRNA-Seq

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Distinct immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell RNA-seq analysis

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Frontiers of Medicine 2024年第1期18卷 147-168页

作者： Weiwei Xian Mohammad Asad Shuai Wu Zhixin Bai Fengjiao Li Junfeng Lu Gaoyu Zu Erin Brintnell Hong Chen Ying Mao Guomin Zhou Bo Liao Jinsong Wu Edwin Wang linya you Department of Human Anatomy&Histoembryology School of Basic Medical SciencesFudan UniversityShanghai200032China Cumming School of Medicine University of CalgaryCalgaryAlbertaT2N 4N1Canada Glioma Surgery Division Department of NeurosurgeryHuashan HospitalFudan UniversityShanghai200040China Department of Pathology Huashan HospitalFudan UniversityShanghai200040China Department of Neurosurgery Huashan HospitalFudan UniversityShanghai200040China Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention Fudan UniversityShanghai200040China School of Mathematics and Statistics Hainan Normal UniversityHaikou570100China

The association of neurogenesis and gliogenesis with glioma remains *** conducting single-cell RNA-seq analyses on 26 gliomas,we reported their classification into primitive oligodendrocyte precursor cell(pri-OPC)-like and radial glia(RG)-like tumors and validated it in a public cohort and TCGA *** RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations,and the pri-OPC-like ones were prone to carrying TP53 *** subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes,suggesting their distinct immune evasion ***,the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct *** specific genes not expressed in normal immune cells were found in glioma-infiltrating *** example,glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes,*** expression was positively correlated with those of immune checkpoint genes(e.g.,LGALS33)and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat *** finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.

关键词： single-cell RNA-seq glioma radial glia primitive oligodendrocyte precursor cell immune escape

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Brpf1 regulates the function of MGE-derived GABAergic interneurons

Brpf1 regulates the function of MGE-derived GABAergic intern...

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中国解剖学会2021年年会

作者： Jingli Cao Weiwei Xian Guomin Zhou linya you Department of Human Anatomy & Histoembryology School of Basic Medical SciencesFudan University

Intellectual disability is a broadspectrum neurodevelopmental disorder characterized by marked impairment of intelligence and adaptive *** GABA neurotransmission is associated with mental disorders such as epilepsy and mental retardation,and patients with BRPF1 mutations were mentally retarded and often accompanied by *** research is to investigate the role of Brpf1 in the development and function of GABAergic interneurons.

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Intellectual disability-related chromatin regulator Brpf1 affects electrophysiological feature of hippocampal neurons and related pathways

Intellectual disability-related chromatin regulator Brpf1 af...

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中国解剖学会2021年年会

作者： Xian Weiwei Yuan Xiangshan Cao Jingli Zhou Guomin you linya Department of Human Anatomy & Histoembryology School of Basic Medical SciencesFudan University

Intellectual disability (ID) is a prevalent neurodevelopmental disorder,affecting 1%-2%of *** researches revealed that haploinsufficiency of Brpfl could result in *** plays important roles in learning and memory which are impaired in people with *** study the roles of Brpf1 in hippocampus, we investigated the morphology,electrophysiology and molecular mechanism in both cultured mouse hippocampal neurons by infecting with AAV-shBrpfl virus and in mouse model by injecting into hippocampal CA1 area with AAV-shBrpfl virus.

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Understandingnormal and diseased human basal ganglia using combinatory indexing single nuclei RNA sequencing

Understandingnormal and diseased human basal ganglia using c...

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中国解剖学会2021年年会

作者： Li Fengjiao Li Peilong Yuan Xiangshan Xian Weiwei Liu Qiong Li Wensheng Zhu Ying you linya Department of Human Anatomy & Histoembryology School of Basic Medical SciencesFudan University Institutes of Brain Sciences Fudan University

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Analysis of cellular diversity and transcriptional regulatory network in human basal ganglia by single cell and bulk RNA sequencing

Analysis of cellular diversity and transcriptional regulator...

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中国解剖学会2021年年会

作者： Li Fengjiao Mohammadi H.B.Asad Yuan Xiangshan Xian Weiwei Liu Qiong Li Wensheng Zhou Guomin Wang Edwin you linya Department of Human Anatomy & Histoembryology School of Basic Medical SciencesFudan University University of Calgary Cumming School of Medicine

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Brpf1 regulates the function of MGE-derived GABAergic interneurons

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解剖学杂志 2021年第S1期44卷 172-172页

作者： Jingli Cao Weiwei Xian Guomin Zhou linya you Department of Human Anatomy&Histoe mbryology School of Basic Medical SciencesFudan UniversityShanghai 200032China

Intellectual disability is a broad-spectrum neurodevelopmental disorder characterized by marked impairment of intelligence and adaptive *** GABA neurotransmission is associated with mental disorders such as epilepsy and mental retardation,and patients with BRPF1 mutations were mentally retarded and often accompanied by *** research is to investigate the role of Brpf1 in the development and function of GABAergic *** used mouse primary in vitro cultured GABAergic interneurons derived from medial ganglionic eminence(MGE)and utilized AAV-shBrpf1 virus to knockdown *** results showed that Brpf1 knockdown led to increased threshold and decreased number of evoked action potentials,and a downward trend of the amplitude and frequency of ***,Brpf1 knockdown had lttle effect on the differentiation of GABAergic interneurons as revealed by parvalbumin and somatostatin ***,little influence on the morphology was observed as shown by MAP2 and Golgi ***,it was found that most of the up-regulated genes are involved in protein binding,ubiquitination,and inflammatory response by RNA Seq.

关键词： epilepsy evoked somatostatin

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Intellectual disability-related chromatin regulator Brpfl affects electrophysiological feature of hippocampal neurons and related pathways

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解剖学杂志 2021年第S1期44卷 136-136页

作者： Xian Weirvei Yuan Xiangshan Cao Jingli Zhou Gruomin you linya Department of Human Anatomy&Histoembryology School of Basic Medical SciencesFudan UniversityShanghai 200032China

Intellectual disability(ID)is a prevalent neurodevelopmental disorder,affecting 1%-2%of *** researches revealed that haploinsufficiency of Brpf1 could result in *** plays important roles in learning and memory which are impaired in people with *** study the roles of Brpf1 in hippocampus,we investigated the morphology,electrophysiology and molecular mechanism in both cultured mouse hippocampal neurons by infecting with AAV-shBrpf1 virus and in mouse model by injecting into hippocampal CA1 area with AAV-shBrpf1 *** results showed that knockdown of Brpf1(at about 50%)reduced the mEPSC frequency and amplitude of cultured hippocampal neurons,though it had no effects on the morphology of these neurons;reduced expression of Brpf1 also downregulated the mRNA level of Syt4,Grik3 and Neurod6,which involved in neuronal excitability;knockdown of Brpf1 in mouse hippocampal CA1 region led to increased expression of Cxcl10,which was related with the death and apoptosis of hippocampal ***,our study found that reduced expression of Brpf1 affected the mEPSC frequency and ampltude of hippocampal neurons as well as dysregulate molecular pathways,which shed new light on Brpfl's role in ID.

关键词： impaired insufficiency hippocampal

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Understandingnormal and diseased human basal ganglia using combinatory indexing single nuclei RNA sequencing

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解剖学杂志 2021年第S1期44卷 72-72页

作者： Li Fengjiao Li Peilong Yuan Xiangshan Xian Weiwei Liu Qiong Li Wensheng Zhu Ying you linya Department of Human Anatomy&Histoembryology School of Basic Medical SciencesFudan UniversityShanghai 200032China Institutes of Brain Sciences Fudan University

With the advent of single cell technology and its rapid applications in the biomedical field,it becomes possible to identify,categorize and characterize each single cell in the *** Brain Bank is accumulating donorbrains very fast(estimately 80 brains till now)from people with normal aging or various neurodegenerative *** basal ganglia is critical for movement control,behavior,cognition,emotion and *** neurodegenerative diseases are related to the abnormality or aging of human basal *** nuclei transcriptomic profiles of both normal and diseased human basal ganglia are still *** our study,we systematically examined different nuclei(caudate,putamen,globus pallidus,and substantia nigra)in human basal ganglia from 6 control and 5 diseased donors(2 psychiatric diseases,2 PD and 1 AD)using combinatory indexing single nuclei RNA *** expression was measured on a total of 22309 control and 42590 diseased single cells.

关键词： indexing normal donor

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Analysis of cellular diversity and transcriptional regulatory network in human basal ganglia by single cell and bulk RNA sequencing

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解剖学杂志 2021年第S1期44卷 70-70页

作者： Li Fengjiao Mohammadi H.B.Asad Yuan Xiangshan Xian Weiwei Liu Qiong Li Wensheng Zhou Guomin Wang Edwin you linya Department of Human Anatomy&Histoe mbryology School of Basic Medical SciencesFudan UniversityShanghai 200032China University of Calgary Cumming School of MedicineCalgaryAlbertaCanada

The basal ganglia is a critical subcortical nuclei in several parallel and closed circuits,which mainly modulate thalamus-cortex *** in any one of these loops connecting cortex can lead to movement and/or mood *** understand cellular complexity,differential gene expression and transcriptional regulatory network of human basal ganglia under normal condition,we performed single cell RNA sequencing of 2424 cells sampled from the basal ganglia of human postmortem brains including caudate,putamen,substantia nigra and globus pallidus.

关键词： cortex network connecting

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