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Dmitry Velmeshev

Assistant Professor of Neurobiology
Neurobiology

Selected Publications


Single-cell analysis of prenatal and postnatal human cortical development.

Journal Article Science · October 13, 2023 We analyzed >700,000 single-nucleus RNA sequencing profiles from 106 donors during prenatal and postnatal developmental stages and identified lineage-specific programs that underlie the development of specific subtypes of excitatory cortical neurons, inter ... Full text Link to item Cite

Astroglial toxicity promotes synaptic degeneration in the thalamocortical circuit in frontotemporal dementia with GRN mutations.

Journal Article J Clin Invest · March 15, 2023 Mutations in the human progranulin (GRN) gene are a leading cause of frontotemporal lobar degeneration (FTLD). While previous studies implicate aberrant microglial activation as a disease-driving factor in neurodegeneration in the thalamocortical circuit i ... Full text Link to item Cite

Cross-regional homeostatic and reactive glial signatures in multiple sclerosis.

Journal Article Acta Neuropathol · November 2022 Multiple sclerosis (MS) is a multifocal and progressive inflammatory disease of the central nervous system (CNS). However, the compartmentalized pathology of the disease affecting various anatomical regions including gray and white matter and lack of appro ... Full text Link to item Cite

Tropism of SARS-CoV-2 for human cortical astrocytes.

Journal Article Proc Natl Acad Sci U S A · July 26, 2022 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. Neurological symptoms, which range in severity, ... Full text Link to item Cite

Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency.

Journal Article Nature · December 2020 Aberrant aggregation of the RNA-binding protein TDP-43 in neurons is a hallmark of frontotemporal lobar degeneration caused by haploinsufficiency in the gene encoding progranulin1,2. However, the mechanism leading to TDP-43 proteinopathy remains unclear. H ... Full text Link to item Cite

Origins and Proliferative States of Human Oligodendrocyte Precursor Cells.

Journal Article Cell · August 6, 2020 Human cerebral cortex size and complexity has increased greatly during evolution. While increased progenitor diversity and enhanced proliferative potential play important roles in human neurogenesis and gray matter expansion, the mechanisms of human oligod ... Full text Link to item Cite

Identification of amygdala-expressed genes associated with autism spectrum disorder.

Journal Article Mol Autism · May 27, 2020 BACKGROUND: Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a range of other phenotypes, implica ... Full text Link to item Cite

Cell-Type-Specific Analysis of Molecular Pathology in Autism Identifies Common Genes and Pathways Affected Across Neocortical Regions.

Journal Article Mol Neurobiol · May 2020 Despite its heterogeneity, autism is characterized by a defined behavioral phenotype, suggesting that the molecular pathology affects specific neural substrates to cause behavioral dysfunction. Previous studies identified genes dysregulated in autism corte ... Full text Link to item Cite

Outer Radial Glia-like Cancer Stem Cells Contribute to Heterogeneity of Glioblastoma.

Journal Article Cell Stem Cell · January 2, 2020 Glioblastoma is a devastating form of brain cancer. To identify aspects of tumor heterogeneity that may illuminate drivers of tumor invasion, we created a glioblastoma tumor cell atlas with single-cell transcriptomics of cancer cells mapped onto a referenc ... Full text Link to item Cite

Neuronal vulnerability and multilineage diversity in multiple sclerosis.

Journal Article Nature · September 2019 Multiple sclerosis (MS) is a neuroinflammatory disease with a relapsing-remitting disease course at early stages, distinct lesion characteristics in cortical grey versus subcortical white matter and neurodegeneration at chronic stages. Here we used single- ... Full text Link to item Cite

Immature excitatory neurons develop during adolescence in the human amygdala.

Journal Article Nat Commun · June 21, 2019 The human amygdala grows during childhood, and its abnormal development is linked to mood disorders. The primate amygdala contains a large population of immature neurons in the paralaminar nuclei (PL), suggesting protracted development and possibly neuroge ... Full text Link to item Cite

Single-cell genomics identifies cell type-specific molecular changes in autism.

Journal Article Science · May 17, 2019 Despite the clinical and genetic heterogeneity of autism, bulk gene expression studies show that changes in the neocortex of autism patients converge on common genes and pathways. However, direct assessment of specific cell types in the brain affected by a ... Full text Link to item Cite

Multimodal Single-Cell Analysis Reveals Physiological Maturation in the Developing Human Neocortex.

Journal Article Neuron · April 3, 2019 In the developing human neocortex, progenitor cells generate diverse cell types prenatally. Progenitor cells and newborn neurons respond to signaling cues, including neurotransmitters. While single-cell RNA sequencing has revealed cellular diversity, physi ... Full text Link to item Cite

Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex.

Journal Article Science · December 8, 2017 Systematic analyses of spatiotemporal gene expression trajectories during organogenesis have been challenging because diverse cell types at different stages of maturation and differentiation coexist in the emerging tissues. We identified discrete cell type ... Full text Link to item Cite

Cocaine alters Homer1 natural antisense transcript in the nucleus accumbens.

Journal Article Mol Cell Neurosci · December 2017 Natural antisense transcripts (NATs) are an abundant class of long noncoding RNAs that have recently been shown to be key regulators of chromatin dynamics and gene expression in nervous system development and neurological disorders. However, it is currentl ... Full text Link to item Cite

Ketamine up-regulates a cluster of intronic miRNAs within the serotonin receptor 2C gene by inhibiting glycogen synthase kinase-3.

Journal Article World J Biol Psychiatry · September 2017 OBJECTIVES: We examined mechanisms that contribute to the rapid antidepressant effect of ketamine in mice that is dependent on glycogen synthase kinase-3 (GSK3) inhibition. METHODS: We measured serotonergic (5HT)-2C-receptor (5HTR2C) cluster microRNA (miRN ... Full text Link to item Cite

Novel Regulatory Mechanisms for the SoxC Transcriptional Network Required for Visual Pathway Development.

Journal Article J Neurosci · May 10, 2017 What pathways specify retinal ganglion cell (RGC) fate in the developing retina? Here we report on mechanisms by which a molecular pathway involving Sox4/Sox11 is required for RGC differentiation and for optic nerve formation in mice in vivo, and is suffic ... Full text Link to item Cite

Single-cell analysis of prenatal and postnatal human cortical development.

Journal Article Science · October 13, 2023 We analyzed >700,000 single-nucleus RNA sequencing profiles from 106 donors during prenatal and postnatal developmental stages and identified lineage-specific programs that underlie the development of specific subtypes of excitatory cortical neurons, inter ... Full text Link to item Cite

Astroglial toxicity promotes synaptic degeneration in the thalamocortical circuit in frontotemporal dementia with GRN mutations.

Journal Article J Clin Invest · March 15, 2023 Mutations in the human progranulin (GRN) gene are a leading cause of frontotemporal lobar degeneration (FTLD). While previous studies implicate aberrant microglial activation as a disease-driving factor in neurodegeneration in the thalamocortical circuit i ... Full text Link to item Cite

Cross-regional homeostatic and reactive glial signatures in multiple sclerosis.

Journal Article Acta Neuropathol · November 2022 Multiple sclerosis (MS) is a multifocal and progressive inflammatory disease of the central nervous system (CNS). However, the compartmentalized pathology of the disease affecting various anatomical regions including gray and white matter and lack of appro ... Full text Link to item Cite

Tropism of SARS-CoV-2 for human cortical astrocytes.

Journal Article Proc Natl Acad Sci U S A · July 26, 2022 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. Neurological symptoms, which range in severity, ... Full text Link to item Cite

Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency.

Journal Article Nature · December 2020 Aberrant aggregation of the RNA-binding protein TDP-43 in neurons is a hallmark of frontotemporal lobar degeneration caused by haploinsufficiency in the gene encoding progranulin1,2. However, the mechanism leading to TDP-43 proteinopathy remains unclear. H ... Full text Link to item Cite

Origins and Proliferative States of Human Oligodendrocyte Precursor Cells.

Journal Article Cell · August 6, 2020 Human cerebral cortex size and complexity has increased greatly during evolution. While increased progenitor diversity and enhanced proliferative potential play important roles in human neurogenesis and gray matter expansion, the mechanisms of human oligod ... Full text Link to item Cite

Identification of amygdala-expressed genes associated with autism spectrum disorder.

Journal Article Mol Autism · May 27, 2020 BACKGROUND: Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a range of other phenotypes, implica ... Full text Link to item Cite

Cell-Type-Specific Analysis of Molecular Pathology in Autism Identifies Common Genes and Pathways Affected Across Neocortical Regions.

Journal Article Mol Neurobiol · May 2020 Despite its heterogeneity, autism is characterized by a defined behavioral phenotype, suggesting that the molecular pathology affects specific neural substrates to cause behavioral dysfunction. Previous studies identified genes dysregulated in autism corte ... Full text Link to item Cite

Outer Radial Glia-like Cancer Stem Cells Contribute to Heterogeneity of Glioblastoma.

Journal Article Cell Stem Cell · January 2, 2020 Glioblastoma is a devastating form of brain cancer. To identify aspects of tumor heterogeneity that may illuminate drivers of tumor invasion, we created a glioblastoma tumor cell atlas with single-cell transcriptomics of cancer cells mapped onto a referenc ... Full text Link to item Cite

Neuronal vulnerability and multilineage diversity in multiple sclerosis.

Journal Article Nature · September 2019 Multiple sclerosis (MS) is a neuroinflammatory disease with a relapsing-remitting disease course at early stages, distinct lesion characteristics in cortical grey versus subcortical white matter and neurodegeneration at chronic stages. Here we used single- ... Full text Link to item Cite

Immature excitatory neurons develop during adolescence in the human amygdala.

Journal Article Nat Commun · June 21, 2019 The human amygdala grows during childhood, and its abnormal development is linked to mood disorders. The primate amygdala contains a large population of immature neurons in the paralaminar nuclei (PL), suggesting protracted development and possibly neuroge ... Full text Link to item Cite

Single-cell genomics identifies cell type-specific molecular changes in autism.

Journal Article Science · May 17, 2019 Despite the clinical and genetic heterogeneity of autism, bulk gene expression studies show that changes in the neocortex of autism patients converge on common genes and pathways. However, direct assessment of specific cell types in the brain affected by a ... Full text Link to item Cite

Multimodal Single-Cell Analysis Reveals Physiological Maturation in the Developing Human Neocortex.

Journal Article Neuron · April 3, 2019 In the developing human neocortex, progenitor cells generate diverse cell types prenatally. Progenitor cells and newborn neurons respond to signaling cues, including neurotransmitters. While single-cell RNA sequencing has revealed cellular diversity, physi ... Full text Link to item Cite

Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex.

Journal Article Science · December 8, 2017 Systematic analyses of spatiotemporal gene expression trajectories during organogenesis have been challenging because diverse cell types at different stages of maturation and differentiation coexist in the emerging tissues. We identified discrete cell type ... Full text Link to item Cite

Cocaine alters Homer1 natural antisense transcript in the nucleus accumbens.

Journal Article Mol Cell Neurosci · December 2017 Natural antisense transcripts (NATs) are an abundant class of long noncoding RNAs that have recently been shown to be key regulators of chromatin dynamics and gene expression in nervous system development and neurological disorders. However, it is currentl ... Full text Link to item Cite

Ketamine up-regulates a cluster of intronic miRNAs within the serotonin receptor 2C gene by inhibiting glycogen synthase kinase-3.

Journal Article World J Biol Psychiatry · September 2017 OBJECTIVES: We examined mechanisms that contribute to the rapid antidepressant effect of ketamine in mice that is dependent on glycogen synthase kinase-3 (GSK3) inhibition. METHODS: We measured serotonergic (5HT)-2C-receptor (5HTR2C) cluster microRNA (miRN ... Full text Link to item Cite

Novel Regulatory Mechanisms for the SoxC Transcriptional Network Required for Visual Pathway Development.

Journal Article J Neurosci · May 10, 2017 What pathways specify retinal ganglion cell (RGC) fate in the developing retina? Here we report on mechanisms by which a molecular pathway involving Sox4/Sox11 is required for RGC differentiation and for optic nerve formation in mice in vivo, and is suffic ... Full text Link to item Cite

Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice.

Journal Article JCI Insight · March 23, 2017 Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve ... Full text Link to item Cite

Deep-RACE: Comprehensive Search for Novel ncRNAs Associated to a Specific Locus.

Chapter · 2017 Deep-RACE (or RACEseq) is a recently described method (Olivarius et al. BioTechniques 46(2):130-132, 2009) that applies next-generation sequencing to the Rapid Amplification of cDNA End (RACE) protocol to define the 5' and 3' ends of RNA transcripts. Conve ... Full text Link to item Cite

Identification of Long Noncoding RNAs Associated to Human Disease Susceptibility.

Chapter · 2017 Transcriptomic as well as in vivo studies have revealed the importance of several lncRNAs in many complex diseases including cancer, cardiovascular, and neurological disorders. In this protocol, we describe how to perform RNAseq data analysis to identify l ... Full text Link to item Cite

A comparative transcriptomic analysis of astrocytes differentiation from human neural progenitor cells.

Journal Article Eur J Neurosci · November 2016 Astrocytes are a morphologically and functionally heterogeneous population of cells that play critical roles in neurodevelopment and in the regulation of central nervous system homeostasis. Studies of human astrocytes have been hampered by the lack of spec ... Full text Link to item Cite

The long non-coding RNA FMR4 promotes proliferation of human neural precursor cells and epigenetic regulation of gene expression in trans.

Journal Article Mol Cell Neurosci · July 2016 Triplet repeat expansions in the Fragile X mental retardation 1 (FMR1) gene cause either intellectual disability and autism, or adult-onset neurodegeneration, with poorly understood variability in presentation. Previous studies have identified several long ... Full text Link to item Cite

CANEapp: a user-friendly application for automated next generation transcriptomic data analysis.

Journal Article BMC Genomics · January 13, 2016 BACKGROUND: Next generation sequencing (NGS) technologies are indispensable for molecular biology research, but data analysis represents the bottleneck in their application. Users need to be familiar with computer terminal commands, the Linux environment, ... Full text Link to item Cite

The BET-Bromodomain Inhibitor JQ1 Reduces Inflammation and Tau Phosphorylation at Ser396 in the Brain of the 3xTg Model of Alzheimer's Disease.

Journal Article Curr Alzheimer Res · 2016 BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by welldefined neuropathological brain changes including amyloid plaques, neurofibrillary tangles and the presence of chronic neuroinflammation. OBJECTIVE: The br ... Full text Link to item Cite

Exogenous Hsp70 delays senescence and improves cognitive function in aging mice.

Journal Article Proc Natl Acad Sci U S A · December 29, 2015 Molecular chaperone Heat Shock Protein 70 (Hsp70) plays an important protective role in various neurodegenerative disorders often associated with aging, but its activity and availability in neuronal tissue decrease with age. Here we explored the effects of ... Full text Link to item Cite

The N-terminal Set-β Protein Isoform Induces Neuronal Death.

Journal Article J Biol Chem · May 22, 2015 Set-β protein plays different roles in neurons, but the diversity of Set-β neuronal isoforms and their functions have not been characterized. The expression and subcellular localization of Set-β are altered in Alzheimer disease, cleavage of Set-β leads to ... Full text Link to item Cite

Transcriptomics Profiling of Alzheimer's Disease Reveal Neurovascular Defects, Altered Amyloid-β Homeostasis, and Deregulated Expression of Long Noncoding RNAs.

Journal Article J Alzheimers Dis · 2015 The underlying genetic variations of late-onset Alzheimer's disease (LOAD) cases remain largely unknown. A combination of genetic variations with variable penetrance and lifetime epigenetic factors may converge on transcriptomic alterations that drive LOAD ... Full text Link to item Cite

Changes in expression of the long non-coding RNA FMR4 associate with altered gene expression during differentiation of human neural precursor cells.

Journal Article Front Genet · 2015 CGG repeat expansions in the Fragile X mental retardation 1 (FMR1) gene are responsible for a family of associated disorders characterized by either intellectual disability and autism Fragile X Syndrome (FXS), or adult-onset neurodegeneration Fragile X-ass ... Full text Link to item Cite

De-repressing LncRNA-Targeted Genes to Upregulate Gene Expression: Focus on Small Molecule Therapeutics.

Journal Article Mol Ther Nucleic Acids · November 18, 2014 Non-protein coding RNAs (ncRNAs) make up the overwhelming majority of transcripts in the genome and have recently gained attention for their complex regulatory role in cells, including the regulation of protein-coding genes. Furthermore, ncRNAs play an imp ... Full text Link to item Cite

Expression of olfactory GPCR signaling genes in the eye (662.15)

Journal Article The FASEB Journal · April 2014 Ocular surface is continuously exposed to particles, microorganisms and other stressors. To advance our understanding how the outer eye interacts with its environment, we asked which cellular receptors are expressed in the cornea, focusing on ident ... Full text Cite

Expression of olfactory signaling genes in the eye.

Journal Article PLoS One · 2014 PURPOSE: To advance our understanding how the outer eye interacts with its environment, we asked which cellular receptors are expressed in the cornea, focusing on G protein-coupled receptors. METHODS: Total RNA from the mouse cornea was subjected to next-g ... Full text Link to item Cite

Expression of non-protein-coding antisense RNAs in genomic regions related to autism spectrum disorders.

Journal Article Mol Autism · September 4, 2013 BACKGROUND: Autism spectrum disorders (ASD) manifest with neurodevelopmental phenotypes including communicative, social and behavioral impairments that affect as many as 1 in 88 children. The majority of autism cases have no known genetic cause, suggesting ... Full text Link to item Cite

Calorie restriction alleviates the age-related decrease in neural progenitor cell division in the aging brain.

Journal Article Eur J Neurosci · June 2013 Production of new neurons from stem cells is important for cognitive function, and the reduction of neurogenesis in the aging brain may contribute to the accumulation of age-related cognitive deficits. Restriction of calorie intake and prolonged treatment ... Full text Link to item Cite