The basal ganglia is a critical subcortical nuclei in several parallel and closed circuits,which mainly modulate thalamus-cortex activity.Dysfunction in any one of these loops connecting cortex can lead to movement an...The basal ganglia is a critical subcortical nuclei in several parallel and closed circuits,which mainly modulate thalamus-cortex activity.Dysfunction in any one of these loops connecting cortex can lead to movement and/or mood disorders.To 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.展开更多
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.Shanghai Brain Bank is accumulatin...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.Shanghai Brain Bank is accumulating donorbrains very fast(estimately 80 brains till now)from people with normal aging or various neurodegenerative diseases.The basal ganglia is critical for movement control,behavior,cognition,emotion and reward.Many neurodegenerative diseases are related to the abnormality or aging of human basal ganglia.Single nuclei transcriptomic profiles of both normal and diseased human basal ganglia are still sparse.In 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 sequencing.Gene expression was measured on a total of 22309 control and 42590 diseased single cells.展开更多
Intellectual disability(ID)is a prevalent neurodevelopmental disorder,affecting 1%-2%of children.Recent researches revealed that haploinsufficiency of Brpf1 could result in ID.Hippocampus plays important roles in lear...Intellectual disability(ID)is a prevalent neurodevelopmental disorder,affecting 1%-2%of children.Recent researches revealed that haploinsufficiency of Brpf1 could result in ID.Hippocampus plays important roles in learning and memory which are impaired in people with ID.To 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 virus.The 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 neurons.Conclusively,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.展开更多
文摘The basal ganglia is a critical subcortical nuclei in several parallel and closed circuits,which mainly modulate thalamus-cortex activity.Dysfunction in any one of these loops connecting cortex can lead to movement and/or mood disorders.To 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.
文摘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.Shanghai Brain Bank is accumulating donorbrains very fast(estimately 80 brains till now)from people with normal aging or various neurodegenerative diseases.The basal ganglia is critical for movement control,behavior,cognition,emotion and reward.Many neurodegenerative diseases are related to the abnormality or aging of human basal ganglia.Single nuclei transcriptomic profiles of both normal and diseased human basal ganglia are still sparse.In 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 sequencing.Gene expression was measured on a total of 22309 control and 42590 diseased single cells.
文摘Intellectual disability(ID)is a prevalent neurodevelopmental disorder,affecting 1%-2%of children.Recent researches revealed that haploinsufficiency of Brpf1 could result in ID.Hippocampus plays important roles in learning and memory which are impaired in people with ID.To 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 virus.The 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 neurons.Conclusively,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.
