Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human iPSC-derived neural progenitor cells secreting GDNF provide protection in rodent models of ALS and retinal degeneration

ABSTRACT: Expanded populations of human fetal-derived neural progenitor cells transduced to produce GDNF (fNPC-GDNF) have now been shown to survive for over three years following injection into the human spinal cord and can provide neuroprotection in many animal models. However, low availability of starting material limits their widespread use. Human induced pluripotent stem cells (iPSCs) are an alternative, renewable cell source that can be differentiated into NPCs and transduced with GDNF (iNPC-GDNF). The goal of the current study was to characterize iNPC-GDNF cells and test their therapeutic potential and safety. Single nuclei RNA- seq showed that fNPC-GDNF and iNPC-GDNF had both overlapping and unique clusters of cells, suggesting that the two products were not identical. When transplanted into the subretinal space of a rodent model of retinal degeneration, iNPC-GDNF preserved photoreceptors and visual function. Transplantation of iNPC-GDNF into the lumbar spinal cord of a rodent model of ALS preserved motor neurons. Finally, to evaluate long-term safety and tolerability, iNPC-GDNF were transplanted into the spinal cord of athymic nude rats for 9 months. Surviving grafts secreting GDNF were found in all animals with no signs of tumor formation or cell proliferation. iNPC-GDNF survive long-term, are safe, and provide neuroprotection in models of both retinal degeneration and ALS, indicating their potential for clinical trials as a cell and gene therapy-based treatment for various neurodegenerative diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214210 | GEO | 2023/04/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Comparison of gene expression in motor pools with differential vulnerability in ALS

Project description:ALS is a uniformly fatal neurodegenerative disease in which motor neurons in the spinal cord and brain stem are selectively lost. Individual motor - groups of motor neurons innervating single muscles - show widely varying degrees of disease resistance: in the final stages of ALS, nearly all voluntary movement is lost but eye movement and eliminative and sexual functions remain relatively unimpaired. These functions are controlled by motor neurons of the oculomotor (III), trochlear (IV) and abducens (VI) nuclei in the midbrain and brainstem, and by Onuf’s nucleus in the lumbosacral spinal cord, respectively. Correspondingly, in ALS autopsies the oculomotor and Onuf’s nuclei are almost completely preserved. We used microarray profiling of isolated wildtype mouse motor neurons to identify genes whose expression was characteristic of both oculomotor and Onuf’s nuclei but not of vulnerable lumbar spinal neurons, or vice versa.

2013-11-15 | GSE52118 | GEO

MS analysis of phosphopeptides enriched from the lumbar spinal cord of SOD1G93A mice at 20weeks.

Project description:This project is "Phosphoproteomic analysis of the lumbar spinal cord, a lesion site in the amyotrophic lateral sclerosis (ALS) mouse model SOD1G93A mice". The aim of this study is to clarify the phosphorylation changes by the lumbar spinal cord of SOD1G93A mice at 20w by applying proteomics technology. The goal of this study is to better understand the pathogenesis of ALS. lumbar spinal cord of SOD1G93A mice (n=5) and WT mice (n=4) were collected at 20w, and the phosphoproteomics were compared.

2022-05-19 | PXD030651 | JPOST Repository

miR-155 plays a crucial role in ALS and is an immune therapeutic target [RNA-Seq]

Project description:Amyotrophic lateral sclerosis (ALS) is a paralytic degenerative disease of the nervous system. In the SOD1 mouse model of ALS we found loss of the molecular and functional microglia signature associated with pronounced expression of miR-155 in SOD1 mice. We also found increased expression of miR-155 in the spinal cord of ALS subjects. Genetic ablation of miR-155 increased survival in SOD1 mice and reversed the abnormal microglial and monocyte molecular signature. In addition, dysregulated proteins in the spinal cord of SOD1 mice that we identified in human ALS spinal cords and CSF were restored in SOD1G93A/miR155-/- mice. Treatment of SOD1 mice with anti-miR-155 SOD1 mice injected systemically or into the cerebrospinal fluid prolonged survival and restored the microglial unique genetic and microRNA profiles. Our findings provide a new avenue for immune based therapy of ALS by targeting miR-155. Total RNA was isolated from whole lumbar spinal cord homogenate from healthy control donors without known neurologic diseases and sporadic and familial ALS.

2014-11-24 | E-GEOD-52946 | biostudies-arrayexpress

Neuronal–Glial Communication Perturbations in Murine SOD1G93A Spinal Cord

Project description:Amyotrophic lateral sclerosis (ALS) is an incurable disease characterized by proteinaceous aggregate accumulation and neuroinflammation culminating in rapidly progressive lower and upper motor neuron death. To interrogate cell-intrinsic and inter-cell type perturbations in ALS, single-nucleus RNA sequencing was performed on the lumbar spinal cord in the murine ALS model SOD1G93A transgenic and littermate control mice at peri-symptomatic onset stage of disease, age 90 days. This work uncovered perturbed tripartite synapse functions, complement activation and metabolic stress in the affected spinal cord; processes evidenced by cell death and proteolytic stress-associated gene sets. Concomitantly, these pro-damage events in the spinal cord co-existed with dysregulated reparative mechanisms. This work provides a resource of cell-specific niches in the ALS spinal cord and asserts that interwoven dysfunctional neuronal-glial communications mediating neurodegeneration are underway prior to overt disease manifestation and are recapitulated, in part, in the human post-mortem ALS spinal cord.

2022-02-18 | GSE173524 | GEO

Transcription profiling of human post mortem spinal cord grey matter from sporadic and familial ALS patients vs controls to identify amyotrophic lateral sclerosis (ALS) associated genes

Project description:Identification of amyotrophic lateral sclerosis (ALS) associated genes. Post mortem spinal cord grey matter from sporadic and familial ALS patients compared with controls.

2007-09-26 | E-GEOD-833 | biostudies-arrayexpress

Early alterations in lipid metabolism in the spinal cord of SOD1 mice

Project description:Amyotrophic lateral sclerosis (ALS) is a multifactorial and complex fatal degenerative disorder. A number of pathological mechanisms that lead to motor neuron death have been identified, although there are many unknowns in the disease aetiology of ALS. Alterations in lipid metabolism are well documented in the progression of ALS, both at the systemic level and in the spinal cord of mouse models and ALS patients. The origin of these lipid alterations remains unclear. This study aims to identify early lipid metabolic pathways altered before systemic metabolic symptoms in the spinal cord of mouse models of ALS. To do this, we performed a transcriptomic analysis of the spinal cord of SOD1G93A mice at an early disease stage(p90)

2021-09-27 | GSE184484 | GEO

Transcription profiling of mouse laser capture microdissected SOD1 G93A motor neurons reveals cellular pathways involved in the adaptation and progression of motor neuron injury in the mouse model of familial ALS

Project description:Microarray analysis has been applied to the study of ALS in order to investigate gene expression in whole spinal cord homogenates of SOD1 G93A mice and human ALS cases, although the massive presence of glial cells and inflammatory factors has made it difficult to define which gene expression changes were motor neuron specific. Recently, laser capture microdissection (LCM), combined with microarray analysis, has allowed the identification of motor neuron specific changes in gene expression in human ALS cases. The aim of the present study is to combine LCM and microarray analysis to study how motor neurons in the spinal cord of transgenic SOD1 G93A mice and transgenic SOD1 WT respond to stimuli determined by the presence of the human mutant protein throughout the evolution of the stages in motor neuron injury Experiment Overall Design: Motor neurons have been isolated from the spinal cord of G93A mice and non transgenic littermates at different time points and the transcription expression profile of the isolated motor neurons has been analysed

2008-06-11 | E-GEOD-10953 | biostudies-arrayexpress

NanoString miRNA profiling of peripheral blood sorted CD14+CD16- monocytes from amyotrophic lateral sclerosis, multiple sclerosis and healthy control subjects

Project description:We investigated the innate immune system in the SOD1 ALS model. We found that splenic Ly6CHi monocytes were activated and their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We found a decrease in resident microglia in the spinal cord with disease progression. Two months prior to disease onset, splenic Ly6CHi monocytes had an M1 signature which included increased CCR2. At one month prior to disease onset, microglia expressed increased CCL2 and other chemotaxis-associated molecules. Microglia derived from the spinal cord of SOD1 mice recruited Ly6C+ monocytes to the CNS. Treatment with anti-Ly6C mAb modulated the Ly6CHi monocyte cytokine profile, reduced monocyte recruitment to the spinal cord, diminished neuronal loss and extended survival. In humans with ALS, CD14+/CD16- monocytes (analogue of Ly6CHi monocytes) exhibited an ALS specific microRNA inflammatory signature similar to that observed in the SOD1 mouse providing a direct link between the animal model and the human disease. Thus, the SOD1-like profile of monocytes in ALS subjects may serve as a biomarker for disease stage or progression. Our results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach. This study used the NanoString nCounter hybridization system and nCounter miRNA expression assays to identify and quantitate miRNAs in blood CD14+CD16- monocytes from ALS, MS and HC subjects Total RNA was isolated from FACS sorted CD14+CD16- blood-derived monocytes from sporadic ALS (n=8), MS (n=8) and HC (n=8) subjects. RNA was profiled using the NanoString nCounter miRNA expression assay

2012-07-25 | E-GEOD-39643 | biostudies-arrayexpress

Amyotrophic lateral sclerosis

Project description:Identification of amyotrophic lateral sclerosis (ALS) associated genes. Post mortem spinal cord grey matter from sporadic and familial ALS patients compared with controls. Keywords: other

2003-11-14 | GSE833 | GEO

Defining the microglia transcriptome during disease progression in ALS transgenic mice

Project description:Purpose: We purified spinal cord microglia utilizing percoll gradients and magnetic beads, followed by transcriptome profiling (RNA-seq) to define microglia expression profiles against other neural, immune cell-types. We next observed how the microglial transcriptomes change during activation in the SOD1-G93A mouse model of motor neuron degeneration at 3 time points. We also compared these profiles with that induced by LPS injection. Results and conclusions: ALS microglia were found to differ substantially from those activated by LPS and from M1/M2 macrophages by comparison with published datasets. These ALS microglia showing substantial induction of a neurodegeneration-tailored phenotype, with induction of lysosomal, RNA splicing, and Alzheimer's disease pathway genes. Overall they express a mixture of neuroprotective and neurotoxic factors during activation in ALS mice, showing that neuro-immune activation in the spinal cord is a double-edged sword. We also detected the transcriptional nature of surface marker expression in microglia (CD11b, CD86, CD11c), and substantial T-cell microglia cross-talk using correlative microglia transcriptome/FACS analysis. 42 total RNA samples from purified spinal cord microglia were subjected to paired-end RNA-sequencing. Parallel flow cytometry data was collected from the same spinal cords.

2013-07-15 | E-GEOD-43366 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data