Senescent astrocytes derived from human pluripotent stem cells reveal age-related changes and implications for neurodegeneration
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE246073 | GEO | 2023/10/28
REPOSITORIES: GEO
Similar Datasets
Project description:Senescent astrocytes derived from human pluripotent stem cells reveal age-related changes and implications for neurodegeneration
| PRJNA1031228 | ENA
Project description:Senescence was recently linked to neurodegeneration. Senescent as well as reactive astrocytes were detected in Parkinson’s disease postmortem brains. This study aimed to determine differences and similarities between senescent and reactive astrocytes. Astrocytes were treated with the stressors hydrogen peroxide or rotenone to induce senescence or with the cytokines TNFa+IL1a or with IL1b to induce reactivity in astrocytes. Comparing the transcriptome of senescent and reactive astrocytes revealed a set of genes specific to senescent astrocytes together with genes regulated in a similar way in both astrocyte states.
2021-06-09 | GSE126750 | GEO
Project description:Transcriptome analysis of senescent and reactive human fetal astrocytes
| PRJNA523186 | ENA
Project description:Differentiation of astrocytes from human pluripotent stem cells (hPSCs) is a tedious and variable process. This hampers the study of hPSC-generated astrocytes in disease processes and drug development. By using CRISPR/Cas9-mediated inducible expression of NFIA or NFIA plus SOX9 in hPSCs, we developed a method to efficiently generate astrocytes in 4-7 weeks. The astrocytic identity of the induced cells was verified by their characteristic molecular and functional properties as well as after transplantation. Furthermore, we developed a strategy to generate region-specific astrocyte subtypes by combining differentiation of regional progenitors and transgenic induction of astrocytes. This simple and efficient method offers a new opportunity to study the fundamental biology of human astrocytes and their roles in disease processes.
2018-08-11 | GSE118384 | GEO
Project description:Senescence is a cellular state linked to aging and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumor formation; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. While senescent cells are active targets for anti-aging therapy, why these cells form in vivo, how they affect tissue aging, and the impact of their elimination remain unclear. Here we identify naturally-occurring senescent glia in aged Drosophila brains and decipher their origin and influence. Using AP1 activity to screen for senescence, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly life and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally-occurring senescent glia in vivo and indicate that these cells link key aging phenomena: mitochondrial dysfunction and lipid accumulation.
2024-05-24 | GSE263928 | GEO
Project description:The ability to generate astrocytes from human pluripotent stem cells (hPSCs) offers a promising cellular model to study the development and physiology of human astrocytes. However, the extant methods for generating functional astrocytes required long culture periods and remained much ambiguity whether their paradigm follows the innate developmental program. In this report, we provided an efficient and rapid method for generating physiologically functional astrocytes from hPSCs. Overexpressing the nuclear factor IB (NFIB) in hPSC-derived neural precursor cells (NPCs) induced a highly enriched astrocyte population in 2 weeks. RNA sequencing and functional analyses demonstrated progressive transcriptomic and physiological changes in the cells, resembling in vivo astrocyte development. Further analyses substantiated previous results and established the MAPK pathway necessary for astrocyte differentiation. Hence, this differentiation paradigm provides a prospective in vitro model for human astrogliogenesis studies and pathophysiology of neurological diseases concerning astrocytes.
2020-09-11 | GSE157768 | GEO
Project description:Astrocytes are key cells in brain aging, helping neurons to undertake healthy aging or otherwise letting them enter into a spiral of neurodegeneration. We aimed to characterize astrocytes cultured from senescence-accelerated prone 8 (SAMP8) mice, a mouse model of brain pathological aging, along with the effects of caloric restriction, the most effective rejuvenating treatment known so far. Analysis of the transcriptomic profiles of SAMP8 astrocytes cultured in control conditions and treated with caloric restriction serum was performed using mRNA microarrays. A decrease in mitochondrial and ribosome mRNA, which was restored by caloric restriction, confirmed the age-related profile of SAMP8 astrocytes and the benefits of caloric restriction. An amelioration of antioxidant and neurodegeneration-related path- ways confirmed the brain benefits of caloric restriction. Studies of oxidative stress and mitochondrial function demonstrated a reduction of oxidative damage and partial improvement of mito- chondria after caloric restriction. In summary, caloric restriction showed a significant tendency to normalize pathologically aged astrocytes through the activation of pathways that are protective against the age-related deterioration of brain physiology. Key words: astrocytes; caloric restriction; mitochondria; oxidative stress; RNA microarrays; SAMP8. Primary cultures enriched in astrocytes were obtained from cerebral cortical tissue from 2-day-old SAMP8 and SAMR1 mice. Astrocyte cultures were established and experiments were routinely carried out after 21 days in culture. Established astrocyte cultures of both SAMR1 and SAMP8 consisted of 85-90% astrocytes, 10-15% microglia and 0.1-1% oligodendroglia. Sera from rats subjected to ad libitum (AL) diet and to CR were obtained as described for the establishment of the CR in vitro model (de Cabo et al., 2003). Serum was heat inactivated at 56°C prior to use in astrocyte culture experiments. Treatment in vitro was performed by adding 10% volume CR or AL serum onto the astrocyte culture medium for 48 h, the cells were harvested and RNA was extracted for the microarray studies. Three biological replicates for each condition were done and RNA was extracted for the microarray studies. Please note that SAM models were developed from AKR/J by Kyoto University. Five litters with severe senescence were selected to further propagate and examine these characteristics. Litters that showed normal aging were selected as a senescence-resistant series (R-series). The genetic background of the SAM mice became suspect after the pathological findings were different from the AKR/J mouse. Each SAM model is genetically different. Each SAM colony was acquired by Harlan by Takeda Chemical Ltd. in 2002. And here is the link to the company site. http://www.harlan.com/products_and_services/research_models_and_services/research_models/sam_inbred_mice/samp8tahsd.hl
2015-06-23 | E-GEOD-60388 | biostudies-arrayexpress
Project description:Through phenotypic drug screening, we identified a novel class of lipid senolytics that selectively eliminated a broad range of senescent cells, reduced tissue senescence, and extended healthspan in mice. Extensive mechanistic studies reveal that these lipids induce ferroptotic cell death by exploiting the iron-rich and ROS-prone characteristics of senescent cells, offering a new therapeutic strategy to target senescence in aging and age-related diseases.
2024-10-07 | GSE278372 | GEO
Project description:Senescence is a cellular state linked to aging and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumor formation; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. While senescent cells are active targets for anti-aging therapy, why these cells form in vivo, how they affect tissue aging, and the impact of their elimination remain unclear. Here we identify naturally-occurring senescent glia in aged Drosophila brains and decipher their origin and influence. Using AP1 activity to screen for senescence, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly life and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally-occurring senescent glia in vivo and indicate that these cells link key aging phenomena: mitochondrial dysfunction and lipid accumulation.
2024-05-24 | GSE263929 | GEO
Project description:Senescence is a cellular state linked to aging and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumor formation; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. While senescent cells are active targets for anti-aging therapy, why these cells form in vivo, how they affect tissue aging, and the impact of their elimination remain unclear. Here we identify naturally-occurring senescent glia in aged Drosophila brains and decipher their origin and influence. Using AP1 activity to screen for senescence, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly life and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally-occurring senescent glia in vivo and indicate that these cells link key aging phenomena: mitochondrial dysfunction and lipid accumulation.
2024-05-24 | GSE263926 | GEO