Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity

Cell, Journal Year: 2020, Volume and Issue: 182(2), P. 388 - 403.e15

Published: July 1, 2020

Language: Английский

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Synaptic Specificity, Recognition Molecules, and Assembly of Neural Circuits

Cell, Journal Year: 2020, Volume and Issue: 181(3), P. 536 - 556

Published: April 1, 2020

Language: Английский

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Mouse Retinal Cell Atlas: Molecular Identification of over Sixty Amacrine Cell Types

Journal of Neuroscience, Journal Year: 2020, Volume and Issue: 40(27), P. 5177 - 5195

Published: May 26, 2020

Amacrine cells (ACs) are a diverse class of interneurons that modulate input from photoreceptors to retinal ganglion (RGCs), rendering each RGC type selectively sensitive particular visual features, which then relayed the brain. While many AC types have been identified morphologically and physiologically, they not comprehensively classified or molecularly characterized. We used high-throughput single-cell RNA sequencing profile >32,000 ACs mice both sexes applied computational methods identify 63 types. molecular markers for them characterize morphology multiple show include nearly all previously known as well had described. Consistent with previous studies, most expressed canonical inhibitory neurotransmitters GABA glycine, but several neither both. In addition, one more neuropeptides, two glutamatergic markers. also explored transcriptomic relationships among transcription factors by individual closely related Noteworthy these were Meis2 Tcf4, GABAergic glycinergic types, respectively. Together, results provide foundation developmental functional studies ACs, means genetically accessing them. Along molecular, physiological, morphologic analyses, establish existence at least 130 neuronal 140 cell in mouse retina. SIGNIFICANCE STATEMENT The retina is leading model analyzing development, structure, function, pathology neural circuits. A complete atlas provides an important studies. heterogeneous interneurons, amacrine cells, identifying distinct includes novel evidence use groups Combining those obtained previously, we proposed contains ∼130 therefore comparable complexity other regions

Language: Английский

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A cell atlas of the chick retina based on single-cell transcriptomics

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Jan. 4, 2021

Retinal structure and function have been studied in many vertebrate orders, but molecular characterization has largely confined to mammals. We used single-cell RNA sequencing (scRNA-seq) generate a cell atlas of the chick retina. identified 136 types plus 14 positional or developmental intermediates distributed among six classes conserved across vertebrates – photoreceptor, horizontal, bipolar, amacrine, retinal ganglion, glial cells. To assess morphology molecularly defined types, we adapted method for CRISPR-based integration reporters into selectively expressed genes. For Müller glia, found that transcriptionally distinct cells were regionally localized along anterior-posterior, dorsal-ventral, central-peripheral axes. also immature horizontal cell, oligodendrocyte persist late embryonic stages. Finally, analyzed relationships chick, mouse, primate types. Our results provide foundation anatomical, physiological, evolutionary, studies avian visual system.

Language: Английский

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Pericytes regulate vascular immune homeostasis in the CNS

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(10)

Published: March 2, 2021

Pericytes regulate the development of organ-specific characteristics brain vasculature such as blood-brain barrier (BBB) and astrocytic end-feet. Whether pericytes are involved in control leukocyte trafficking adult central nervous system (CNS), a process tightly regulated by CNS vasculature, remains elusive. Using pericyte-deficient mice (Pdgfbret/ret ), we show that limit infiltration into during homeostasis autoimmune neuroinflammation. The permissiveness toward Pdgfbret/ret inversely correlates with vessel pericyte coverage. Upon induction experimental encephalomyelitis (EAE), die severe atypical EAE, which can be reversed fingolimod, indicating mortality is due to massive influx immune cells brain. Additionally, administration anti-VCAM-1 anti-ICAM-1 antibodies reduces diminishes severity EAE symptoms mice, proinflammatory endothelium absence facilitates exaggerated Furthermore, presence myelin peptide-specific peripheral T ;2D2tg leads spontaneous neurological paralleled leukocytes These findings indicate intrinsic changes within promote neuroinflammatory disorder.

Language: Английский

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Integrating barcoded neuroanatomy with spatial transcriptional profiling enables identification of gene correlates of projections

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(6), P. 873 - 885

Published: May 10, 2021

Language: Английский

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Molecular classification of zebrafish retinal ganglion cells links genes to cell types to behavior

Neuron, Journal Year: 2020, Volume and Issue: 109(4), P. 645 - 662.e9

Published: Dec. 23, 2020

Language: Английский

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Trans-Seq maps a selective mammalian retinotectal synapse instructed by Nephronectin

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(5), P. 659 - 674

Published: May 1, 2022

Language: Английский

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Spatial organization of the mouse retina at single cell resolution by MERFISH

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 15, 2023

The visual signal processing in the retina requires precise organization of diverse neuronal types working concert. While single-cell omics studies have identified more than 120 different subtypes mouse retina, little is known about their spatial organization. Here, we generated atlas using multiplexed error-robust fluorescence situ hybridization (MERFISH). We profiled over 390,000 cells and all major cell nearly through integration with reference RNA sequencing (scRNA-seq) data. Our allowed simultaneous examination revealing 8 previously unknown displaced amacrine establishing connection between molecular classification many arrangement. Furthermore, spatially dependent differential gene expression subtypes, suggesting possibility functional tuning based on location.

Language: Английский

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A highly reproducible and efficient method for retinal organoid differentiation from human pluripotent stem cells

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(25)

Published: June 13, 2024

Human pluripotent stem cell (hPSC)-derived retinal organoids are three-dimensional cellular aggregates that differentiate and self-organize to closely mimic the spatial temporal patterning of developing human retina. Retinal organoid models serve as reliable tools for studying retinogenesis, yet limitations in efficiency reproducibility current differentiation protocols have reduced use these more high-throughput applications such disease modeling drug screening. To address shortcomings, study aimed standardize prior yield a highly reproducible efficient method generating organoids. Results demonstrated through regulation size shape using quick reaggregation methods, were compared traditional methods. Additionally, timed activation BMP signaling within cells generated pure populations at 100% from multiple widely used lines, with default forebrain fate resulting inhibition signaling. Furthermore, given ability direct or fates complete purity, mRNA-seq analyses then utilized identify some earliest transcriptional changes occur during specification two lineages common progenitor. These improved methods also yielded expedited timelines when Taken together, results this demonstrate development minimally variable suitable analyzing stages specification.

Language: Английский

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