Generation of functional posterior spinal motor neurons from hPSCs-derived human spinal cord neural progenitor cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA847229 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19586400_1.fastq.gz | Fastqsanger.gz | |||
| SRR19586400_2.fastq.gz | Fastqsanger.gz | |||
| SRR19586401_1.fastq.gz | Fastqsanger.gz | |||
| SRR19586401_2.fastq.gz | Fastqsanger.gz | |||
| SRR19586402_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 132 |
Similar Datasets
Project description:Spinal motor neurons deficiency results in a series of devastating disorders such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and spinal cord injury (SCI). These devastating disorders are currently incurable, while human pluripotent stem cells (hPSCs) derived spinal motor neurons are promising but suffered by low-efficiency, functional immaturity and lacks of posterior cell identity. In this study, we have established human spinal cord neural progenitor cells (hSCNPCs) via hPSCs differentiated neuromesodermal progenitors (NMPs) and demonstrated the hSCNPCs can be continuously expanded up to 40 passages. hSCNPCs can be rapidly differentiated into posterior spinal motor neurons with high efficiency. The functional maturity has been examined in detail. Moreover, a co-culture scheme which is compatible for both neural and muscular differentiation is developed to mimic the neuromuscular junction (NMJ) formation in vitro. Together, these studies highlight the potential avenues for generating clinically relevant motor neurons and modelling neuromuscular diseases through our defined hSCNPCs.
2023-06-01 | GSE205718 | GEO
Project description:Spinal cord injuries (SCI) result in the loss of motor and sensory function. We are working towards restoring sensation by developing directed differentiation protocols to generate dorsal spinal interneurons (dIs; dI1-dI6) from human embryonic stem cells (hESCs). Here, we present an improved method that produces human dIs via a neuromesodermal progenitor state, the physiological intermediate for spinal cord development. We show that retinoic acid (RA), bone morphogenetic protein 4 (BMP4) and growth differentiation factor (GDF) 11 direct dI identity, while GDF11 and extended time in culture promotes posterior spinal identities. Together, these protocols generate the full complement of dorsal subtypes along the entire anterior-posterior axis of the spinal cord. To benchmark in vitro-derived dIs, we constructed a single-cell RNA-Seq atlas of the human embryonic spinal cord and used it to show that hESC-derived dIs closely match their endogenous counterparts. The atlas also reveals that the dI4/dI5 populations dramatically expand in comparison with the other spinal lineages. Moreover, they have mechanosensory circuit signatures linked to autism spectrum disorder, implicating spinal circuits in autistic phenotypes.
2026-04-01 | GSE326655 | GEO
Project description:Spinal cord injuries (SCI) result in the loss of motor and sensory function. We are working towards restoring sensation by developing directed differentiation protocols to generate dorsal spinal interneurons (dIs; dI1-dI6) from human embryonic stem cells (hESCs). Here, we present an improved method that produces human dIs via a neuromesodermal progenitor state, the physiological intermediate for spinal cord development. We show that retinoic acid (RA), bone morphogenetic protein 4 (BMP4) and growth differentiation factor (GDF) 11 direct dI identity, while GDF11 and extended time in culture promotes posterior spinal identities. Together, these protocols generate the full complement of dorsal subtypes along the entire anterior-posterior axis of the spinal cord. To benchmark in vitro-derived dIs, we constructed a single-cell RNA-Seq atlas of the human embryonic spinal cord and used it to show that hESC-derived dIs closely match their endogenous counterparts. The atlas also reveals that the dI4/dI5 populations dramatically expand in comparison with the other spinal lineages. Moreover, they have mechanosensory circuit signatures linked to autism spectrum disorder, implicating spinal circuits in autistic phenotypes.
2026-04-01 | GSE326654 | GEO
Project description:Spinal cord injuries (SCI) result in the loss of motor and sensory function. We are working towards restoring sensation by developing directed differentiation protocols to generate dorsal spinal interneurons (dIs; dI1-dI6) from human embryonic stem cells (hESCs). Here, we present an improved method that produces human dIs via a neuromesodermal progenitor state, the physiological intermediate for spinal cord development. We show that retinoic acid (RA), bone morphogenetic protein 4 (BMP4) and growth differentiation factor (GDF) 11 direct dI identity, while GDF11 and extended time in culture promotes posterior spinal identities. Together, these protocols generate the full complement of dorsal subtypes along the entire anterior-posterior axis of the spinal cord. To benchmark in vitro-derived dIs, we constructed a single-cell RNA-Seq atlas of the human embryonic spinal cord and used it to show that hESC-derived dIs closely match their endogenous counterparts. The atlas also reveals that the dI4/dI5 populations dramatically expand in comparison with the other spinal lineages. Moreover, they have mechanosensory circuit signatures linked to autism spectrum disorder, implicating spinal circuits in autistic phenotypes.
2026-04-01 | GSE326652 | GEO
Project description:Spinal cord injuries (SCI) result in the loss of motor and sensory function. We are working towards restoring sensation by developing directed differentiation protocols to generate dorsal spinal interneurons (dIs; dI1-dI6) from human embryonic stem cells (hESCs). Here, we present an improved method that produces human dIs via a neuromesodermal progenitor state, the physiological intermediate for spinal cord development. We show that retinoic acid (RA), bone morphogenetic protein 4 (BMP4) and growth differentiation factor (GDF) 11 direct dI identity, while GDF11 and extended time in culture promotes posterior spinal identities. Together, these protocols generate the full complement of dorsal subtypes along the entire anterior-posterior axis of the spinal cord. To benchmark in vitro-derived dIs, we constructed a single-cell RNA-Seq atlas of the human embryonic spinal cord and used it to show that hESC-derived dIs closely match their endogenous counterparts. The atlas also reveals that the dI4/dI5 populations dramatically expand in comparison with the other spinal lineages. Moreover, they have mechanosensory circuit signatures linked to autism spectrum disorder, implicating spinal circuits in autistic phenotypes.
2026-04-01 | GSE326651 | GEO
Project description:Patients with spinal cord injuries often suffer from multiple complications, including cognitive impairments after recovering from the primary wound. The molecular mechanism linking spinal cord injury and brain abnormality, however, remains elusive and has been largely attributed to neuroinflammation. In this work, we assessed persistent compositional and molecular changes in the motor cortex at 30 days post injury, a commonly perceived chronic stage, using a rat T10 contusion injury model. Brain slices and neurons isolated from the motor cortex were assessed using immunohistochemistry and RNA-sequencing, respectively. We observed significant changes in cellular compositions in the motor cortex including a decreased neuron to astrocyte ratio, and alterations in the morphology of neurons and astrocytes, indicating changes in functionality. Comparison of transcriptomic data collected at a sub-acute stage, namely 7 days post injury, with that at 30 days post injury, identified persistent and de novo (genes uniquely altered at 30 dpi.) changes that occur primarily after recovery of the spinal cord injury, enriched for neuronal and synaptic function related pathways. Strikingly, male and female rats showed distinct transcriptomic alterations at 30 days post-injury, with males showing neuron-related changes and females showing alterations in metabolism- and extracellular matrix–related pathways. These molecular differences were accompanied by better functional recovery in females, as reflected by significantly higher BBB scores, suggesting sex-dependent molecular changes induced in the motor cortex. Collectively, our study lays the foundation for understanding sexual dimorphism in brains after spinal cord injury and provides a plausible connection between spinal cord injury and increased risk for neurodegeneration later in life.
2026-04-06 | GSE326470 | GEO
Project description:Motor neurons are a rare neuronal subtype in the adult spinal cord. We performed single-nucleus RNA sequencing on nuclei extracted from adult human spinal cord and describe the transcriptional heterogeneity.
2023-04-06 | GSE228778 | GEO
Project description:In our original grant we proposed to use the NR3B-null mouse model to study the role of NR3B subunit in motor neuron function. We have now successfully generated NR3B null mice. Interestingly, NR3B-null mice invariably die at age P4-P8. Our preliminary examination indicates that the motor strength of these mice is severely impaired prior to death. As we continue to explore the cause of death in NR3B null mice, we propose to conduct gene profiling experiments to search for transcription changes in the brain related to ablation of the NR3B gene. We have used the facility provided by the NINDS/NIMH Microarray Consortium to identify genes that show abnormal expression patterns in these mice. We would like to compare these changes with that opccured in SOD1 mice, a mouse model of motor neuron diseases. Analysis of these genes will help to identify changes in networks and pathways that may cause the death of NR3B-null mice. These studies will further help to elucidate the functional role of NR3B in motor neurons. We will compare samples from motor neurons of wild type and SOD1 mice to identify genes that show abnormal expression patterns, which may be implicated in the death of SOD1 mice and shared with the same changes in NR3B-null mice. We hypothesize that genes with their transcription level changing significantly by ablation of NR3B will be associated with the molecular mechanism underlying the death of motor neurons in NR3B null mice. As NR3B is expressed primarily in the motor neurons of hindbrain and spinal cord, we have first collected and analyzed the spinal cord samples from NR3B null mice and wild-type controls in P4, an age of disease onset. We like to compare motor neuron and spinal cord smaples from SOD1 mice at the age prior to the disease onset. Total RNA from total 12 samples will be purified from ~200 motor neurons obtained by Laser Capture Microdissection and the total spinal cord. Extracted RNAs will be subjected to one or two rounds of amplification and the obtained cRNA will be biotinylated. The purified cRNA will be sent to the NINDS/NIMH Microarray Consortium be used to hybridize the GeneChip Mouse Genome 430 2.0 Array. The hybridization, scanning, and initial data analysis of these GeneChips will be conducted by the Consortium staff. We will analyze the collected data further after data collection. We will first identify genes that show significant changes between wild-type and SOD1 mice and then compare that with the result from NR3B null mice.
2008-06-13 | E-GEOD-5037 | biostudies-arrayexpress
Project description:The chicken spinal cord is a classic model system to study the early specification of neuronal cell types along its anterior-posterior axis. Here, we follow the ensuing maturation dynamics at limb levels with single cell resolution and contrast neuronal populations innervating appendages of distinct form and function. We use gene co-expression modules to identify rare cell populations with specific biological functions, and show that appendages with different motor outputs – wings and legs – rely on largely similar spinal cord cell type repertoires. Challenging the system with experimental alterations to the peripheral limb musculature reveals limited transcriptional changes, but spatially restricted plasticity in spinal cord motor neuron numbers. Collectively, our results provide a resource to investigate the molecular and cellular basis of neuronal maturation in the avian spinal cord and highlight the plastic nature of embryonic cells to adapt to changes in the limb periphery at both developmental and evolutionary timescales.
2026-02-09 | GSE297980 | GEO
Project description:Spinal cord injury leads to impaired motor and sensory functions. After spinal cord injury there is a an initial phase of hypo-reflexia followed by a developing hyper-reflexia, often termed spasticity. Previous studies have suggested a relationship between the reappearence of plateau potentials in motor neurons and the development of spasticity after spinalization. To understand the molecular mechanism behind this phenomenon we examined the transcriptional response of the motor neurons after spinal cord injury. We used a rat tail injury model where a complete transection of the caudal (S2) rat spinal cord leads to an immidate flaccid paralysis of the tail and a subsequent appearence of spasticity 2-3 weeks post injury that develops into strong spasticity after 2 months. Gene expression changes were studied in motor neurons 21 and 60 days after complete spinal transection where the tail exhibits clear signs of spasticity. Tail MNs were retorgradely labelled with flourogold injected into the muscle and intra peritoneally. 5-7 days after tracer injections the spinal cord was dissected out, snab frozen in liquid nitrogen, sliced in 10 um thick slices and fluorescent motor neurons were laser dissected into a collector tube to a total of ca. 50-200 cells pr sample. RNA was then extracted, two round amplified and hybridized to Affymetrix rat 230 2.0 arays. 27 samples were hybridized onto chips, 8 Spi-21, 8 Spi-60, 6 ShamC-21 and 5 ShamC-60.
2009-10-31 | E-GEOD-16710 | biostudies-arrayexpress