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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE215174 | GEO | 2023/12/31

REPOSITORIES: GEO

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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

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

| PRJNA889031 | ENA

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

Age-associated changes in microglia and astrocytes ameliorate blood-brain barrier dysfunction.

Project description:Blood-brain barrier (BBB) dysfunction is associated with an accumulation of neurotoxic molecules and increased infiltration of peripheral cells within the brain parenchyma. Accruing evidence suggests that microglia and astrocytes play a crucial role in the recovery of BBB integrity and the corralling of infiltrating cells into clusters after brain damage, but the mechanisms involved remain unclear. Intriguingly, the results of flow cytometry and immunofluorescence analyses have shown that BBB permeability to peripheral cells is substantially enhanced during normal aging at 12 months in mice. Thus, we used the SMART-seq2 method to perform RNA sequencing of microglia and astrocytes at five time points before and immediately after the BBB permeability change. Our comprehensive analyses revealed that microglia are characterized by marked alterations in the negative regulation of protein phosphorylation and phagocytic vesicles, whereas astrocytes show elevated enzyme or peptidase-inhibitor activity in the recovery of BBB function. Moreover, we identified a cassette of key genes that might ameliorate the insults of pathophysiological events in aging and neurodegenerative disease.

| S-EPMC8561003 | biostudies-literature

Transplantation of Human Brain Organoids: Revisiting the Science and Ethics of Brain Chimeras.

Project description:Recent demonstrations of human brain organoid transplantation in rodents have accentuated ethical concerns associated with these entities, especially as they relate to potential "humanization" of host animals. Consideration of established scientific principles can help define the realistic range of expected outcomes in such transplantation studies. This practical approach suggests that augmentation of discrete brain functions in transplant hosts is a more relevant ethical question in the near term than the possibility of "conscious" chimeric animals. We hope that this framework contributes to a balanced approach for proceeding with studies involving brain organoid transplantation and other forms of human-animal brain chimeras.

| S-EPMC7180006 | biostudies-literature

Cerebral organoids transplantation improves neurological motor function in rat brain injury.

Project description:Background and purposeCerebral organoids (COs) have been used for studying brain development, neural disorders, and species-specific drug pharmacology and toxicology, but the potential of COs transplantation therapy for brain injury remains to be answered.MethodsWith preparation of traumatic brain injury (TBI) model of motor dysfunction, COs at 55 and 85 days (55 and 85 d-CO) were transplanted into damaged motor cortex separately to identify better transplantation donor for brain injury. Further, the feasibility, effectiveness, and underlying mechanism of COs transplantation therapy for brain injury were explored.Results55 d-CO was demonstrated as better transplantation donor than 85 d-CO, evidenced by more neurogenesis and higher cell survival rate without aggravating apoptosis and inflammation after transplantation into damaged motor cortex. Cells from transplanted COs had the potential of multilinage differentiation to mimic in-vivo brain cortical development, support region-specific reconstruction of damaged motor cortex, form neurotransmitter-related neurons, and migrate into different brain regions along corpus callosum. Moreover, COs transplantation upregulated hippocampal neural connection proteins and neurotrophic factors. Notably, COs transplantation improved neurological motor function and reduced brain damage.ConclusionsThis study revealed 55 d-CO as better transplantation donor and demonstrated the feasibility and efficacy of COs transplantation in TBI, hoping to provide first-hand preclinical evidence of COs transplantation for brain injury.

| S-EPMC7298981 | biostudies-literature

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