Parkinson's disease(PD)is a neurodegenerative disease,leading to the impairment of movement execution.PD pathogenesis has been largely investigated,either limited to bulk transcriptomic levels or at certain cell t...Parkinson's disease(PD)is a neurodegenerative disease,leading to the impairment of movement execution.PD pathogenesis has been largely investigated,either limited to bulk transcriptomic levels or at certain cell types,which failed to capture the cellular heterogeneity and intrinsic interplays among distinct cell types.Here,we report the application of single-nucleus RNA-seq on midbrain,striatum,and cerebellum of theα-syn-A53 T mouse,a well-established PD mouse model,and matched controls,generating the first single cell transcriptomic atlas for the PD model mouse brain composed of 46,174 individual cells.Additionally,we comprehensively depicte the dysfunctions in PD pathology,covering the elevation of NF-k B activity,the alteration of ion channel components,the perturbation of protein homeostasis network,and the dysregulation of glutamatergic signaling.Notably,we identify a variety of cell types closely associated with PD risk genes.Taken together,our study provides valuable resources to systematically dissect the molecular mechanism of PD pathogenesis at the single-cell resolution,which facilitates the development of novel approaches for diagnosis and therapies against PD.展开更多
Olfaction,the sense of smell,is a fundamental trait crucial to many species.The olfactory bulb(OB)plays pivotal roles in processing and transmitting odor information from the environment to the brain.The cellular hete...Olfaction,the sense of smell,is a fundamental trait crucial to many species.The olfactory bulb(OB)plays pivotal roles in processing and transmitting odor information from the environment to the brain.The cellular heterogeneity of the mouse OB has been studied using single-cell RNA sequencing.However,the epigenetic landscape of the m OB remains mostly unexplored.Herein,we apply single-cell assay for transposaseaccessible chromatin sequencing to profile the genome-wide chromatin accessibility of 9,549 single cells from the m OB.Based on single-cell epigenetic signatures,m OB cells are classified into 21 clusters corresponding to 11 cell types.We identify distinct sets of putative regulatory elements specific to each cell cluster from which putative target genes and enriched potential functions are inferred.In addition,the transcription factor motifs enriched in each cell cluster are determined to indicate the developmental fate of each cell lineage.Our study provides a valuable epigenetic data set for the m OB at single-cell resolution,and the results can enhance our understanding of regulatory circuits and the therapeutic capacity of the OB at the single-cell level.展开更多
The brain of the domestic pig(Sus scrofa domesticus)has drawn considerable attention due to its high similarities to that of humans.However,the cellular compositions of the pig brain(PB)remain elusive.Here we investig...The brain of the domestic pig(Sus scrofa domesticus)has drawn considerable attention due to its high similarities to that of humans.However,the cellular compositions of the pig brain(PB)remain elusive.Here we investigated the single-nucleus transcriptomic profiles of five regions of the PB(frontal lobe,parietal lobe,temporal lobe,occipital lobe,and hypothalamus)and identified 21 cell subpopulations.The cross-species comparison of mouse and pig hypothalamus revealed the shared and specific gene expression patterns at the single-cell resolution.Furthermore,we identified cell types and molecular pathways closely associated with neurological disorders,bridging the gap between gene mutations and pathogenesis.We reported,to our knowledge,the first single-cell atlas of domestic pig cerebral cortex and hypothalamus combined with a comprehensive analysis across species,providing extensive resources for future research regarding neural science,evolutionary developmental biology,and regenerative medicine.展开更多
Severe volume expansion of silicon(Si)leads to unstable solid electrolyte interface(SEI)rupture and electrode structure collapse,ultimately causing poor cycling stability of lithium-ion batteries.Herein,we engineered ...Severe volume expansion of silicon(Si)leads to unstable solid electrolyte interface(SEI)rupture and electrode structure collapse,ultimately causing poor cycling stability of lithium-ion batteries.Herein,we engineered a hydroxyl-rich silicon surface,enhancing the interface forces by increasing hydrogen bonding sites with carboxymethyl cellulose(CMC),thereby maintaining a mechanical balance during dynamic volume change.Furthermore,theoretical calculations indicate that the augmentation of hydroxyl groups promotes the charge transfer between the CMC molecule and the surface and enhances the interface adsorption energy.As a result,the obtained Si-C_(2)H_(6)O anode exhibits a high specific capacity of 2483 mA h g^(−1) at 0.2 A g^(−1) after 100 cycles,with a capacity retention of 81.2%.In addition,it exhibits a durable specific capacity of above 1200 mA h g^(−1) at 2 A g^(−1) after 1000 cycles with a coulombic efficiency of over 99.5%.The assembled full cells based on the Si-C_(2)H_(6)O anode achieve a high areal capacity of 2.68 mA h cm−2 at 0.2 C.The success of this strategy effectively addresses the issue of volume expansion in Si anodes,further enhancing the cycling performance and facilitating their wide-scale commercial applications.展开更多
基金supported by the National Natural Science Foundation of China(31702074 and 31872309)Sanming Project of Medicine in Shenzhen(SZSM202011012)Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20170412153100794)。
文摘Parkinson's disease(PD)is a neurodegenerative disease,leading to the impairment of movement execution.PD pathogenesis has been largely investigated,either limited to bulk transcriptomic levels or at certain cell types,which failed to capture the cellular heterogeneity and intrinsic interplays among distinct cell types.Here,we report the application of single-nucleus RNA-seq on midbrain,striatum,and cerebellum of theα-syn-A53 T mouse,a well-established PD mouse model,and matched controls,generating the first single cell transcriptomic atlas for the PD model mouse brain composed of 46,174 individual cells.Additionally,we comprehensively depicte the dysfunctions in PD pathology,covering the elevation of NF-k B activity,the alteration of ion channel components,the perturbation of protein homeostasis network,and the dysregulation of glutamatergic signaling.Notably,we identify a variety of cell types closely associated with PD risk genes.Taken together,our study provides valuable resources to systematically dissect the molecular mechanism of PD pathogenesis at the single-cell resolution,which facilitates the development of novel approaches for diagnosis and therapies against PD.
基金supported by Shenzhen Sanming Engineering Project(SZSM202011012)Shenzhen Innovation Science and Technology Committee(JCYJ20180228175358223)National Natural Science Foundation of China(31670742)。
文摘Olfaction,the sense of smell,is a fundamental trait crucial to many species.The olfactory bulb(OB)plays pivotal roles in processing and transmitting odor information from the environment to the brain.The cellular heterogeneity of the mouse OB has been studied using single-cell RNA sequencing.However,the epigenetic landscape of the m OB remains mostly unexplored.Herein,we apply single-cell assay for transposaseaccessible chromatin sequencing to profile the genome-wide chromatin accessibility of 9,549 single cells from the m OB.Based on single-cell epigenetic signatures,m OB cells are classified into 21 clusters corresponding to 11 cell types.We identify distinct sets of putative regulatory elements specific to each cell cluster from which putative target genes and enriched potential functions are inferred.In addition,the transcription factor motifs enriched in each cell cluster are determined to indicate the developmental fate of each cell lineage.Our study provides a valuable epigenetic data set for the m OB at single-cell resolution,and the results can enhance our understanding of regulatory circuits and the therapeutic capacity of the OB at the single-cell level.
基金the China Postdoctoral Science Foundation(2017M622795)the Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20180507183628543)the Fundamental Research Funds for the Central Universities(2662018PY025 and 2662017PY105)。
文摘The brain of the domestic pig(Sus scrofa domesticus)has drawn considerable attention due to its high similarities to that of humans.However,the cellular compositions of the pig brain(PB)remain elusive.Here we investigated the single-nucleus transcriptomic profiles of five regions of the PB(frontal lobe,parietal lobe,temporal lobe,occipital lobe,and hypothalamus)and identified 21 cell subpopulations.The cross-species comparison of mouse and pig hypothalamus revealed the shared and specific gene expression patterns at the single-cell resolution.Furthermore,we identified cell types and molecular pathways closely associated with neurological disorders,bridging the gap between gene mutations and pathogenesis.We reported,to our knowledge,the first single-cell atlas of domestic pig cerebral cortex and hypothalamus combined with a comprehensive analysis across species,providing extensive resources for future research regarding neural science,evolutionary developmental biology,and regenerative medicine.
基金support provided by the National Natural Science Foundation of China(No.22175059,21875061,21975066)the Open Research Fund Program of the National Key Laboratory of Aerospace Chemical Power,Hubei Institute of Aerospace Chemotechnology(No.STACPL 120221B06).
文摘Severe volume expansion of silicon(Si)leads to unstable solid electrolyte interface(SEI)rupture and electrode structure collapse,ultimately causing poor cycling stability of lithium-ion batteries.Herein,we engineered a hydroxyl-rich silicon surface,enhancing the interface forces by increasing hydrogen bonding sites with carboxymethyl cellulose(CMC),thereby maintaining a mechanical balance during dynamic volume change.Furthermore,theoretical calculations indicate that the augmentation of hydroxyl groups promotes the charge transfer between the CMC molecule and the surface and enhances the interface adsorption energy.As a result,the obtained Si-C_(2)H_(6)O anode exhibits a high specific capacity of 2483 mA h g^(−1) at 0.2 A g^(−1) after 100 cycles,with a capacity retention of 81.2%.In addition,it exhibits a durable specific capacity of above 1200 mA h g^(−1) at 2 A g^(−1) after 1000 cycles with a coulombic efficiency of over 99.5%.The assembled full cells based on the Si-C_(2)H_(6)O anode achieve a high areal capacity of 2.68 mA h cm−2 at 0.2 C.The success of this strategy effectively addresses the issue of volume expansion in Si anodes,further enhancing the cycling performance and facilitating their wide-scale commercial applications.
