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Single cell analysis of the ventricular-subventricular zone reveals signatures of dorsal and ventral adult neurogenic lineages. [single nucleus sequencing]

ABSTRACT: Purpose: While great progress has been made in understanding the differences in regional stem cell potential using viral and genetic lineage tracing strategies, the core molecular heterogeneity that underlies these regional differences is largely unknown. Methods: Here we present a single nucleus sequencing dataset of four microdissected regions of adult CD1 wild type mouse ventricular-subventricular zones (V-SVZ). Four samples (anterior-ventral, AV; anterior dorsal, AD; posterior ventral, PV; posterior dorsal, PD) were generated at the same time from the same mice, and each sample was run on its own lane of a 10x Chromium Single Cell Controller chip for single nucleus barcoding. Results: Here we present single nucleus and single whole cell sequencing datasets of microdissected adult mouse V-SVZ, and evidence for the existence of two broad subtypes of adult neural stem cells. By using spatially resolved microdissections in the single nucleus sequencing dataset as a reference, and mapping marker gene expression in the V-SVZ, we find that these two populations reside in largely non-overlapping domains in either the dorsal or ventral V-SVZ. Furthermore, we identified two subpopulations of newly born neurons that have gene expression consistent with dorsal or ventral origins. Finally, we identify genes expressed by both stem cells and the neurons they generate that specifically mark either the dorsal or ventral adult neurogenic lineage. These datasets, methods and findings will enable future study of region-specific regulation of adult neurogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE165551 | GEO | 2021/02/10

REPOSITORIES: GEO

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Single cell analysis of the ventricular-subventricular zone reveals signatures of dorsal and ventral adult neurogenic lineages. [single whole-cell]

Project description:Purpose: While great progress has been made in understanding the differences in regional stem cell potential using viral and genetic lineage tracing strategies, the core molecular heterogeneity that underlies these regional differences is largely unknown. Methods: Here we present a single whole-cell sequencing dataset of microdissected adult hGFAP:GFP mouse V-SVZ. Four samples were (two samples from male mice, two samples from female mice) multiplexed & combined using MULTI-Seq barcodes (McGinnes et al. 2019), labeled with TotalSeq antibodies against VCAM1 and CD24 proteins (Biolegend), and were split into two technical replicate lanes on a 10x Chromium Single Cell Controller chip for single cell barcoding. Genomic libraries were prepared using standard Illumina protocols, and barcode libraries (MULTI-Seq, TotalSeq) were prepared using MULTI-Seq protocols. Results: Here we present single whole-cell and single nucleus sequencing datasets of microdissected adult mouse V-SVZ, and evidence for the existence of two broad subtypes of adult neural stem cells. By using spatially resolved microdissections in the single nucleus sequencing dataset as a reference, and mapping marker gene expression in the V-SVZ, we find that these two populations reside in largely non-overlapping domains in either the dorsal or ventral V-SVZ. Furthermore, we identified two subpopulations of newly born neurons that have gene expression consistent with dorsal or ventral origins. Finally, we identify genes expressed by both stem cells and the neurons they generate that specifically mark either the dorsal or ventral adult neurogenic lineage. These datasets, methods and findings will enable future study of region-specific regulation of adult neurogenesis.

2021-02-10 | GSE165554 | GEO

Transcriptional profiling by array of chick embryonic tissues: gastrulation, neural tube/notochord and limb development.

Project description:Microarray analysis of chick embryo tissues: Hamburger Hamilton (HH) stage 3+/4 and HH6 Hensenâs node, HH 3+/4 posterior primitive streak, notochord with ventral neural tube at HH10-11, dorsal neural tube at HH10-11 and anterior and posterior thirds of the wing bud at stages HH20-21 and HH24.

2016-08-23 | E-MTAB-4048 | biostudies-arrayexpress

A Non-Canonical Raf Function Is Required for Dorsal-Ventral Patterning in Drosophila Embryogenesis

Project description:Embryonic development requires the establishment of directional axes. In Drosophila, spatially discrete expression of transcription factors determines the anterior to posterior organization of the early embryo, while the Toll and TGF-beta signalling pathways determine the early dorsal to ventral pattern. Embryonic MAPK/ERK signaling contributes to both anterior to posterior patterning in the terminal regions and to dorsal to ventral patterning during oogenesis and embryonic stages. Here we describe a novel loss of function mutation in the Raf kinase gene, which leads to loss of ventral cell fates as seen through the loss of the ventral furrow, the absence of Dorsal/NF-kB nuclear localization, the absence of mesoderm determinants Twist and Snail, and the expansion of TGF-beta. Gene expression analysis showed cells adopting ectodermal fates similar to loss of Toll signaling. Our results combine novel mutants, live imaging, optogenetics and transcriptomics to establish a novel role for Raf, that appears to be independent of the MAPK cascade, in embryonic patterning.

2021-08-03 | GSE178187 | GEO

Proteomic profile of hippocampus regions from the pilocarpine medial temporal lobe epilepsy model

Project description:Label-free Proteomic profile of the dentate gyrus (dorsal and ventral) and CA3 (dorsal and ventral) microdissected from the hippocampus of the pilocarpine model of Mesial Temporal Lobe Epilepsy.

2024-03-25 | MSV000094401 | MassIVE

A Single-Cell Atlas of Cell Types, States, and Other Transcriptional Patterns from Nine Regions of the Adult Mouse Brain

Project description:We report 690K single-cell transcriptomes from nine different brain regions from adult mice (Frontal and Posterior Cortex, Hippocampus, Thalamus, Cerebellum, Striatum, Globus Pallidus externus/Nucleus Basalis, Entopeduncular / Subthalamic Nuclei, & Substantia Nigra / Ventral Tegmental Area).

2018-08-22 | GSE116470 | GEO

Rat Normal Cochlear Nucleus

2006-01-01 | GSE3628 | GEO

Rat Normal Cochlear Nucleus

Project description:The cochlear nucleus is the first central pathway involved in the processing of peripheral auditory activity. It is heterogeneous in neuronal populations and physiologic responses and is organized in three major subdivisions: the anterior ventral cochlear nucleus (AVCN), the posterior ventral cochlear nucleus (PVCN) and the dorsal cochlear nucleus (DCN). Although each region demonstrates multiple cell types and functions, there are predominant populations of neurons in each region that underlie the principal role each subdivision plays in auditory processing. Little is known of the underlying genetic contribution to these properties. This study sought to identify genes expressed in the subdivisions of the cochlear nucleus that may account for the anatomical and physiological characteristics of each subdivision. These data provide a genetic basis for understanding normal auditory processing in the cochlear nucleus and a template for investigating changes that may occur with hearing loss, the generation and percept of tinnitus, and central processing disorders. Keywords: normal, comparative Brown Norway rats (n=40, female, 45days) were anesthetized and decapitated. Brains were rapidly removed and the subdivisions of the cochlear nucleus (AVCN, PVCN and DCN) dissected on dry ice. Total RNA was extracted and tested for concentration and purity by spectrophotometry and integrity by gel electrophoresis. SAGE was performed using the NlaIII enzyme and Invitrogen SAGE kit. Concatemers were commercially sequenced and imported into eSAGE (Margulies and Innis, 2000) for tag extraction and frequency.

2005-12-31 | E-GEOD-3628 | biostudies-arrayexpress

Adult Mouse Leptomeninges Exhibit Regional and Age-related Cellular Heterogeneity Implicating Mental Disorders

Project description:Transplantation of retinal pigment epithelial (RPE) cells holds great promise for RPE tissue repair in patients with retinal degenerative diseases, such as age-related macular The leptomeninges envelop the central nervous system (CNS) and contribute to cerebrospinal fluid (CSF) production and homeostasis. We analyzed the meninges overlying the anterior or posterior forebrain in the adult mouse by single nuclear RNA-sequencing (snucRNA-seq). This revealed regional differences in fibroblast and endothelial cell composition and gene expression. Surprisingly, these non-neuronal cells co-expressed genes implicated in neural functions. The regional differences changed with aging, from 3 to 18 months. Cytokine analysis revealed specific soluble factor production from anterior vs posterior meninges that also altered with age. Secreted factors from the leptomeninges from different regions and ages differentially impacted the survival of anterior or posterior cortical neuronal subsets, neuron morphology, and glia proliferation. These findings suggest that meningeal dysfunction in different brain regions could contribute to specific neural pathologies. The disease-associations of meningeal cell genes differentially expressed with region and age were significantly enriched for mental and substance abuse disorders.

2023-09-10 | GSE242810 | GEO

Single-muscle-cell transcriptome profiling along the planarian anteroposterior axis

Project description:How positional information instructs adult tissue maintenance is poorly understood. Planarians undergo whole-body regeneration and tissue turnover, providing a model for adult positional information studies. Genes encoding secreted and transmembrane components of multiple developmental pathways are predominantly expressed in planarian muscle cells. Several of these genes regulate regional identity, consistent with muscle harboring positional information. Here, single-cell RNA-sequencing of 115 muscle cells from distinct anterior-posterior regions identified 44 regionally expressed genes, including multiple Wnt and ndk/FGF receptor-like (ndl/FGFRL) genes. Two distinct FGFRL-Wnt circuits, involving juxtaposed anterior FGFRL and posterior Wnt expression domains, controlled planarian head and trunk patterning. ndl-3 and wntP-2 inhibition expanded the trunk, forming ectopic mouths and secondary pharynges, which independently extended and ingested food. fz5/8-4 inhibition, like that of ndk and wntA, caused posterior brain expansion and ectopic eye formation. Our results suggest that FGFRL-Wnt circuits operate within a body-wide coordinate system to control adult axial positioning.

2016-04-12 | GSE74360 | GEO

A Molecular Atlas of the Developing Ectoderm Defines Neural, Neural Crest, Placode and Non-Neural Progenitor Identity in Vertebrates.

Project description:During vertebrate neurulation, the embryonic ectoderm is patterned into lineage progenitors for neural plate, neural crest, placodes and epidermis. Here, we use Xenopus laevis embryos to analyze the spatial and temporal transcriptome of distinct ectodermal domains in the course of neurulation, during the establishment of cell lineages. In order to define the transcriptome of small groups of cells from a single germ layer, and to retain spatial information, dorsal and ventral ectoderm was subdivided along the anterior-posterior and medial-lateral axes by microdissections. Principal Component Analysis on the transcriptomes of these ectoderm fragments primarily identifies embryonic axes and temporal dynamics. This provides a genetic code to define positional information of any ectoderm sample along the anterior-posterior and dorsal-ventral axes, directly from its transcriptome. In parallel, we use Non-Negative Matrix Factorization to predict enhanced gene expression maps onto early and mid-neurula embryos, and specific signatures for each ectoderm area. The clustering of spatial and temporal datasets allowed detection of multiple biologically relevant groups (e.g. Wnt signaling, neural crest development, sensory placode specification, ciliogenesis, germ layer specification). We provide an interactive network interface, EctoMap, for exploring synexpression relationships among genes expressed in the neurula, and suggest several strategies to use this comprehensive dataset to address questions in developmental biology as well as stem cell or cancer research.

2017-10-25 | GSE103240 | GEO

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