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Genome-wide analysis of three clonal neural stem cell lines derived from human foetal spinal cord tissue.

ABSTRACT: Stem cells have received substantial interest both for their potential as in vitro tools to study development and as potential therapeutic agents in a range of degenerative diseases of the nervous system. We have generated clonal neural stem cell lines from human foetal spinal cord conditionally immortalised with 4-hydroxy tamoxifen inducible cMyc (cMycERTAM), and performed a detailed assessment of their identity in terms of their expression of homeodomain transcription factors and their capacity to generate particular neuronal subtypes of the spinal cord. These lines retain a ventral spinal cord progenitor phenotype and give rise to electrically active neuronal subtypes characteristic of specific ventral progenitor subdomains. Upon grafting into lesioned rat spinal cord these cells differentiate into ChAT+ve motorneurons and show robust survival after 4 months.

ORGANISM(S): Homo sapiens

PROVIDER: GSE37282 | GEO | 2012/06/16

SECONDARY ACCESSION(S): PRJNA159397

REPOSITORIES: GEO

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Genome-wide analysis of three clonal neural stem cell lines derived from human foetal spinal cord tissue.

Project description:Stem cells have received substantial interest both for their potential as in vitro tools to study development and as potential therapeutic agents in a range of degenerative diseases of the nervous system. We have generated clonal neural stem cell lines from human foetal spinal cord conditionally immortalised with 4-hydroxy tamoxifen inducible cMyc (cMycERTAM), and performed a detailed assessment of their identity in terms of their expression of homeodomain transcription factors and their capacity to generate particular neuronal subtypes of the spinal cord. These lines retain a ventral spinal cord progenitor phenotype and give rise to electrically active neuronal subtypes characteristic of specific ventral progenitor subdomains. Upon grafting into lesioned rat spinal cord these cells differentiate into ChAT+ve motorneurons and show robust survival after 4 months. Total RNA was obtained from three proliferative undifferentiated neural stem cell lines at 75% confluence in culture. Two replicates of each clonal line were generated for microarray analysis.

2012-06-15 | E-GEOD-37282 | biostudies-arrayexpress

Single-cell transcription mapping of neural subtype development in human spinal cord

Project description:The spinal cord possesses precise neural circuitry to transmit messages between the brain and body. Detailed transcriptomic profiling of the developing human spinal cord has not been reported. Here, we performed single cell RNA sequencing of developing human spinal cord cells and compared these data with similar mouse spinal cord RNA sequencing datasets. The differentiation tendency of proliferative neural progenitor cells changed from neuronal to glial cells at gestational week (GW) 8 and we identified a diverse set of excitatory, inhibitory and motor neuron cell types. Human ventral neuronal differentiation occurred earlier than GW7, while DI4/5 interneurons are born between GW7–11. We identified glial cell molecular diversity and revealed that ependymal cell specification occurs before birth. We also demonstrate differences between human and mouse spinal cord, including unique cell subtypes, gene expression, neurotransmitter receptors, and glial differentiation timing. Our results offer insight into human spinal cord development.

2021-10-27 | GSE136719 | GEO

Single-nucleus transcriptomic atlas of spinal cord neuron in human

Project description:Despite the recognized importance of the spinal cord in sensory processing, motor behaviors, and/or neural diseases, the underlying organization of neuronal clusters remain elusive. Recently, several studies have attempted to define the neuronal types and functional heterogeneity in the spinal cord using single-cell and/or single-nucleus RNA-sequencing in various animal models. However, molecular evidence of neuronal heterogeneity in the human spinal cord has not yet been established. Here, we sought to classify spinal cord neurons from human donors using high-throughput single-nucleus RNA-sequencing. The functional heterogeneity among the identified cell types and signaling pathways that connect neuronal subtypes were explored. Moreover, we compared the transcriptional patterns obtained in human samples with previously published single-cell transcriptomic profiles of the mouse spinal cord. As a result, we generated the first comprehensive transcriptomic atlas of human spinal cord neurons and defined 18 neuronal clusters. In addition to identifying new and functionally distinct neuronal subtypes, our results also provide novel marker genes for previously described neuronal types. The comparison with mouse transcriptomic profiles revealed an overall similarity in the cellular composition of the spinal cord between the two species, while simultaneously highlighting some degree of heterogeneity. In summary, these results illustrate the complexity and diversity of neuronal types in the human spinal cord and provide an important resource for future research to explore the molecular mechanisms underlying spinal cord physiology and diseases.

2022-11-07 | GSE188255 | GEO

Global Transcriptional analysis of human spinal cord and neocortical neuroepithelial stem (NES) cells

Project description:We report the transcriptional profile of human spinal cord and neocortical neuroepithelial stem cells (SC-NES and NCX-NES cells) to identify potential engraftment markers in the lesioned spinal cord. We report that cells with a homologous neuroanatomical origin robustly integrate in the host tissue compared to cells with a different regional identity. Specifically, we describe that SC-NES cells display elective integration properties in the lesioned spinal cord compared to NCX-NES cells and that these properties are due to a combination of intrinsic and extrinsic factors. Upon transplantation, SC-NES cells differentiate into neurons and glial cells and extend lond-distance axons, whereas NCX-NES cells remain undifferentiated and display poor integration properties. SC-NES cell upregulate genes related to neurogenesis. In particular. we emphasize the upregulation of MTURN (maturin), ATCAY, PTN (pleiotropin), KAL1 (anosmin), SYT4 and SYT13.

2018-08-29 | GSE107514 | GEO

Astrocyte-encoded positional cues maintain sensorimotor circuit integrity

Project description:Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restricted astrocytes are functionally heterogeneous. Here we show that postnatal spinal cord astrocytes express several region-specific genes, and that ventral astrocyte-encoded Semaphorin3a (Sema3a) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded Sema3a led to dysregulated α−motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of α−but not of adjacent γ−motor neurons. Additionally, a subset of TrkA+ sensory afferents projected to ectopic ventral positions. These findings demonstrate that stable maintenance of a positional cue by developing astrocytes influences multiple aspects of sensorimotor circuit formation. More generally, they suggest that regional astrocyte heterogeneity may help to coordinate postnatal neural circuit refinement. 12 total samples consisting of three biological replicates each of flow sorted postnatal day 7 dorsal spinal cord astrocytes, ventral spinal cord astrocytes, dorsal SC non astrocytes, and ventral SC non astrocytes

2014-05-02 | E-GEOD-55054 | biostudies-arrayexpress

Transcription profiling of rat lumbar spinal cord following ventral root avulsion in two inbred strains to investigate susceptibility to neurodegeneration

Project description:Gene expression profiling in rat lumbar spinal cord following ventral root avulsion in the two inbred rat strains.

2006-08-15 | E-MEXP-671 | biostudies-arrayexpress

Patterns of gene Expression during the Spinal cord Injury/Regeneration

Project description:Spinal cord injury (SCI) induces a sequence of endogenous autodestructive changes known as secondary injury, as well as reactive biochemical changes that are neuroprotective and/or promote recovery. All these responses to SCI are, in part re?ected in changes in gene expression. In order to assess changes in gene expression involved in the regeneration process,microarrays were performed as a function of time after SCI for the various treatments. Three groups rats(i.e.NT-3-chitosan tube group, tube alone group and lesion control group) used to interrogate Affymetrix (SantaClara,CA) GeneChips were sacrificed by intraperitoneally over dose injecting 6% chloral hydrate at 1, 3, 10, 20, 30, and 90 d after the operation. The spinal cords were surgically re-exposed and spinal tissue including dura and meninges was dissected into three blocks, i.e. 5 mm long segments in the lesioned area (M), rostral to the lesioned area (R), and caudal to the lesioned areas (C) were sampled under RNAase-free conditions. The samples were quick frozen and kept in liquid nitrogen.

2012-01-01 | E-GEOD-29488 | biostudies-arrayexpress

Muscle expression of SOD1G93A modulates microRNA and mRNA expression pattern associated with the myelination process in the spinal cord of transgenic mice [RT-PCR]

Project description:Expression profile of microRNA in lumbar spinal cord from MLC/SOD1G93A using Applied Biosystem Array Mouse MicroRNA A Card Lumbar Spinal Cord Ventral samples were collected from mice MLC/SOD1[G93A] and control FVB age matched at 4 month-old. Samples were collected for RNA extraction and analyzed on Taqman Array Mouse MicroRNA Card A version 3.0

2015-12-31 | E-GEOD-71193 | biostudies-arrayexpress

Hyperbaric oxygen therapy after mid-cervical spinal contusion injury

Project description:Hyperbaric oxygen (HBO) therapy is frequently used to treat peripheral wounds or decompression sickness. Evidence suggests that HBO therapy can provide neuroprotection and has an anti-inflammatory impact after neurologic injury including spinal cord injury (SCI). Our primary purpose was to conduct an unbiased, genome-wide screening of mRNA expression changes in the injured spinal cord after HBO therapy. A mRNA gene array was used to evaluate samples taken from the contused region of the spinal cord following a lateralized mid-cervical contusion injury in adult female rats. HBO therapy consisted of daily, 1-hour sessions (3.0 ATA, 100% O2) initiated on the day of SCI. Gene set enrichment analyses indicated that HBO upregulated genes in pathways associated with electron transport, mitochondrial function, and oxidative phosphorylation, and downregulation genes in pathways associated with inflammation (including cytokines and NF-B) and apoptotic signaling. In a separate cohort, spinal cord histology was performed to verify whether the HBO treatment impacted neuronal cell counts or inflammatory markers. Compared to untreated rats, there was increased NeuN positive cells in the spinal cord of HBO treated rats (p=0.007). Further, staining for anti-ionized calcium binding adaptor protein (Iba-1, a microglial marker) was reduced after HBO (p=0.028). We conclude that HBO therapy, initiated shortly after SCI and continued for 10-days, can alter the molecular signature of the lesioned spinal cord in a manner consistent with an anti-inflammatory and neuroprotective impact.

2022-05-18 | GSE185600 | GEO

Repression by PRDM13 is critical for generating precise neuronal identity (RNA-Seq)

Project description:The mechanisms that activate some genes while silencing others are critical to ensure precision in lineage specification as multipotent progenitors become restricted in cell fate. During neurodevelopment, these mechanisms are required to generate the wide variety of neuronal subtypes found in the nervous system. Here we report interactions between basic helix-loop-helix (bHLH) transcriptional activators and the transcriptional repressor PRDM13 that are critical for these processes during specification of dorsal spinal cord neurons. PRDM13 inhibits gene expression programs for the excitatory neuronal lineages in the dorsal neural tube while also suppressing a battery of genes that determine ventral neural tube fates including Olig1, Olig2 and Prdm12. PRDM13 does this via recruitment to chromatin by multiple neural bHLH factors to restrict gene expression in specific neuronal lineages. Together these findings highlight the function of PRDM13 in repressing bHLH transcriptional activators that together are required to achieve precise neuronal specification during development.

2017-08-04 | GSE90937 | GEO

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