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Hypothalamus-specific NSCs derived from human brain organoids ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus

ABSTRACT: Hypothalamus-specific NSCs derived from human brain organoids ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus

PROVIDER: PRJNA889031 | ENA |

REPOSITORIES: ENA

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Hypothalamus-specific NSCs derived from human brain organoids ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus [mouse]

Project description:The hypothalamus is the brain region that regulates systemic body metabolism and multiple functions in other brain regions. In adult mice, the hypothalamus harbors neural stem/precursor cell (NSC)-like cells. Along with the dysregulation of body metabolism and physiology that occurs during aging, the NSC population in the hypothalamus declines with age. Here, we introduce a novel protocol that yields scalable and storable hypothalamus-specific NSCs (htNSCs) from hypothalamus-like organoids derived from human pluripotent stem cells (hPSCs). Implanting htNSCs into the medio-basal hypothalami of aged mice conspicuously ameliorated age-related declines in metabolic fitness, physical capacity, and cognitive function and produced corresponding histologic changes in various body tissues. Single transcriptome and immunohistochemical analyses of the grafted hypothalamic tissues showed that the anti-aging effects were attained by correcting glial NF-κB, TNFα, and NLRP3 inflammasome pathways. Collectively, our findings support the potential of anti- or healthy aging therapies that target htNSCs and hypothalamic inflammation.

2023-12-31 | GSE214896 | GEO

Hypothalamus-specific NSCs derived from human brain organoids ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus [human]

2023-12-31 | GSE215173 | GEO

Hypothalamus-specific NSCs derived from human brain organoids ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus [human bulk RNAseq]

2022-10-11 | GSE214877 | GEO

Hypothalamus-specific NSCs derived from human brain organoids ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus [human]

Project description:Hypothalamus-specific NSCs derived from human brain organoids ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus [human]

| PRJNA889034 | ENA

Hypothalamus-specific NSCs derived from human brain organoids ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus [mouse]

Project description:Hypothalamus-specific NSCs derived from human brain organoids ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus [mouse]

| PRJNA887685 | ENA

Hypothalamus-specific NSCs derived from human brain organoids ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus [human bulk RNAseq]

Project description:Hypothalamus-specific NSCs derived from human brain organoids ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus [human bulk RNAseq]

| PRJNA887453 | ENA

Hypothalamus-specific NSCs derived from human brain organoids ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-12-31 | GSE215174 | GEO

Genome-wide profiling of hypothalamus, cerebellum, striatum, and frontal cortex across young, middle-aged, and aged mice

Project description:We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. Compared to young mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance) impairments. In contrast, aged BALB mice exhibit marked energy balance (but not locomotor) impairments. Age-related changes in cerebellar or hypothalamic gene expression accompany these phenotypes. Aging evokes upregulation of immune pattern recognition receptors and cell adhesion molecules. However, these changes do not localize to microglia, the major CNS immunocyte. Consistent with a neuronal role, there is a marked age-related increase in excitatory synapses over the cerebellum and hypothalamus. Functional imaging of these regions is consistent with age-related synaptic impairments. These studies suggest that aging reactivates a developmental program employed during embryogenesis where immune molecules guide synapse formation and pruning. Renewed activity in this program may disrupt excitatory neurotransmission, causing significant behavioral deficits. keywords: aging, C57BL/6, BALB, CBA, hypothalamus, cerebellum, striatum, frontal cortex

2016-09-20 | GSE87102 | GEO

Enhanced functional recovery from spinal cord injury in aged mice after stem cell transplantation through HGF induction

Project description:The number of elderly patients with spinal cord injury (SCI) is increasing worldwide, representing a serious burden for both the affected patients and the community. Previous studies have demonstrated that neural stem cell (NSC) transplantation is an effective treatment for SCI in young animals. Here we show that NSC transplantation is as effective in aged mice as it is in young mice, even though aged mice exhibit more severe neurological deficits after SCI. NSCs grafted into aged mice exhibited better survival than did those grafted into young mice. Furthermore, we show that the neurotrophic factor HGF plays a key role in the enhanced functional recovery after NSC transplantation observed in aged mice with SCI. The unexpected results of the present study suggest that NSC transplantation is a potential therapeutic modality for SCI, even in elderly patients.

2017-01-13 | GSE93561 | GEO

Gene expression data from mouse ES cell-derived primitive NSCs and definitive NSCs

Project description:Primitive neural stem cells (NSCs) could be derived from pluripotent mouse embryonic stem (ES) cells, and then differentiate into definitive-type neural stem cells which resemble NSCs obtained from the central nervous system. Hence, primitive NSCs define an early stage of neural induction and provide a model to understand the mechanism that controls initial neural commitment. In this study, we performed microarray assay to analyze the global transcriptional profiles in mouse ES cell-derived primitive and definitive NSCs and to depict the molecular changes during the multi-staged neural differentiation process. Primitive NSCs derived directly from ESCs in Lif (p-NSC_L), primitive NSCs that were sub-cultured in the presence of Lif and FGF (p-NSC_LF), as well as definitive NSCs derived from primitive NSCs in medium containing FGF and EGF, were collected for RNA extraction and hybridization on Affymetrix microarrays. Mouse ESCs and NSCs obtained from mouse embryonic brain (E11.5) were included for controls. For each cell type, we collected two biological replicate samples for microarray analysis.

2014-03-01 | E-GEOD-44608 | biostudies-arrayexpress

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