Neurotherapeutics, Год журнала: 2024, Номер unknown, С. e00493 - e00493
Опубликована: Ноя. 1, 2024
Язык: Английский
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Июль 28, 2024
Abstract The ability to spatially map multiple layers of the omics information over different time points allows for exploring mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC–RNA–Protein-seq) CTRP-seq CUT&Tag– RNA–Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) dynamic remodeling development neuroinflammation. A spatiotemporal atlas mouse was obtained at stages from postnatal day P0 P21, compared regions interest human developing brains. Specifically, cortical area, discovered temporal persistence spreading chromatin accessibility layer-defining transcription factors. In corpus callosum, observed priming myelin genes across subregions. Together, it suggests a role layer specific projection neurons coordinate axonogenesis myelination. We further mapped lysolecithin (LPC) neuroinflammation model common molecular programs Microglia, exhibiting both conserved distinct inflammation resolution, are transiently activated not only core LPC lesion, but also distal locations presumably through neuronal circuitry. Thus, this work unveiled differential neuroinflammation, resulting valuable data resource investigate function
Язык: Английский
Процитировано
20
Frontiers in Psychiatry, Год журнала: 2024, Номер 15
Опубликована: Ноя. 15, 2024
Multiple lines of evidence indicate that altered dopamine signaling may be involved in neuropsychiatric disorders and common behavioral traits. Here we critically review collected during the past 40-plus years supporting role dysfunction attention deficit hyperactivity disorder (ADHD). We recapitulate basic components dopaminergic central nervous system, focusing on core enzymes, transporters receptors monoaminergic functions, particularly striatal cortical regions. summarize key human brain imaging genetic studies reporting associations between neurotransmission traits, with an emphasis ADHD. also consider ADHD context animal models single gene, metabolic, neurological established system. Examining this way leads us to conclude there is for involvement but limited a hypo-dopaminergic state per se as component propose path forward increase our understanding traits should focus its clinical subgroups, development how it interacts other neurotransmitter systems.
Язык: Английский
Процитировано
10
Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Авг. 12, 2024
The ability to spatially map multiple layers of the omics information over different time points allows for exploring mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC-RNA-Protein-seq) CTRP-seq CUT&Tag-RNA-Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) dynamic remodeling development neuroinflammation. A spatiotemporal atlas mouse was obtained at stages from postnatal day P0 P21, compared regions interest human developing brains. Specifically, cortical area, discovered temporal persistence spreading chromatin accessibility layer-defining transcription factors. In corpus callosum, observed priming myelin genes across subregions. Together, it suggests a role layer specific projection neurons coordinate axonogenesis myelination. We further mapped lysolecithin (LPC) neuroinflammation model common molecular programs Microglia, exhibiting both conserved distinct inflammation resolution, are transiently activated not only core LPC lesion, but also distal locations presumably through neuronal circuitry. Thus, this work unveiled differential neuroinflammation, resulting valuable data resource investigate function
Язык: Английский
Процитировано
6
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Фев. 8, 2025
Abstract A critical phase of mammalian brain development takes place after birth. Neurons the mouse neocortex undergo dramatic changes in their morphology, physiology, and synaptic connections during first postnatal month, while properties immature neurons, such as capacity for robust axon outgrowth, are lost. The genetic epigenetic programs controlling prenatal well studied, but our understanding transcriptional mechanisms that regulate neuronal maturation is comparatively lacking. By integrating chromatin accessibility gene expression data from two subtypes neocortical pyramidal neurons neonatal maturing brain, we predicted a role Krüppel-Like Factor (KLF) family Transcription Factors developmental regulation neonatally expressed genes. Using multiplexed CRISPR Interference (CRISPRi) knockdown strategy, found shift KLF activators (Klf6, Klf7) to repressors (Klf9, Klf13) early functions ‘switch’ activate, then repress set shared targets with cytoskeletal including Tubb2b Dpysl3 . We demonstrate this switch buffered by redundancy between paralogs, which CRISPRi strategy equipped overcome study. Our results indicate competition within regulates conserved component program may underlie loss intrinsic growth neurons. This could facilitate transition refinement required stabilize mature circuits.
Язык: Английский
Процитировано
0
Опубликована: Апрель 30, 2025
A critical phase of mammalian brain development takes place after birth. Neurons the mouse neocortex undergo dramatic changes in their morphology, physiology, and synaptic connections during first postnatal month, while properties immature neurons, such as capacity for robust axon outgrowth, are lost. The genetic epigenetic programs controlling prenatal well studied, but our understanding transcriptional mechanisms that regulate neuronal maturation is comparatively lacking. By integrating chromatin accessibility gene expression data from two subtypes neocortical pyramidal neurons neonatal maturing brain, we predicted a role Krüppel-Like Factor (KLF) family Transcription Factors developmental regulation neonatally expressed genes. Using multiplexed CRISPR Interference (CRISPRi) knockdown strategy, found shift KLF activators (Klf6, Klf7) to repressors (Klf9, Klf13) early functions ‘switch’ activate, then repress set shared targets with cytoskeletal including Tubb2b Dpysl3 . We demonstrate this switch buffered by redundancy between paralogs, which CRISPRi strategy equipped overcome study. Our results indicate competition within regulates conserved component program may underlie loss intrinsic growth neurons. This could facilitate transition refinement required stabilize mature circuits.
Язык: Английский
Процитировано
0
Опубликована: Апрель 30, 2025
A critical phase of mammalian brain development takes place after birth. Neurons the mouse neocortex undergo dramatic changes in their morphology, physiology, and synaptic connections during first postnatal month, while properties immature neurons, such as capacity for robust axon outgrowth, are lost. The genetic epigenetic programs controlling prenatal well studied, but our understanding transcriptional mechanisms that regulate neuronal maturation is comparatively lacking. By integrating chromatin accessibility gene expression data from two subtypes neocortical pyramidal neurons neonatal maturing brain, we predicted a role Krüppel-Like Factor (KLF) family Transcription Factors developmental regulation neonatally expressed genes. Using multiplexed CRISPR Interference (CRISPRi) knockdown strategy, found shift KLF activators (Klf6, Klf7) to repressors (Klf9, Klf13) early functions ‘switch’ activate, then repress set shared targets with cytoskeletal including Tubb2b Dpysl3 . We demonstrate this switch buffered by redundancy between paralogs, which CRISPRi strategy equipped overcome study. Our results indicate competition within regulates conserved component program may underlie loss intrinsic growth neurons. This could facilitate transition refinement required stabilize mature circuits.
Язык: Английский
Процитировано
0
The Transmitter, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
0
Neuroscience & Biobehavioral Reviews, Год журнала: 2024, Номер 167, С. 105936 - 105936
Опубликована: Ноя. 6, 2024
Язык: Английский
Процитировано
0
Neurotherapeutics, Год журнала: 2024, Номер unknown, С. e00493 - e00493
Опубликована: Ноя. 1, 2024
Язык: Английский
Процитировано
0