Diverse maturity-dependent and complementary anti-apoptotic brakes safeguard human iPSC-derived neurons from cell death [scRNA-seq]
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ABSTRACT:
PROVIDER: PRJNA857905 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20084538_1.fastq.gz | Fastqsanger.gz | |||
| SRR20084538_2.fastq.gz | Fastqsanger.gz |
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Project description:Diverse maturity-dependent and complementary anti-apoptotic brakes safeguard human iPSC-derived neurons from cell death.
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Project description:Diverse maturity-dependent and complementary anti-apoptotic brakes safeguard human iPSC-derived neurons from cell death [RNA-seq]
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Project description:In humans, most neurons are born during embryonic development and have to persist throughout the entire lifespan of an individual. Thus, human neurons have to develop elaborate survival strategies to protect against accidental cell death. We set out to decipher the developmental adaptations resulting in neuronal resilience. We demonstrate that, during the time course of maturation, human neurons install a complex and complementary anti-apoptotic signaling network. This includes i.) a downregulation of central proteins of the intrinsic apoptosis pathway including several caspases, ii.) a shift in the ratio of pro- and anti-apoptotic BCL-2 family proteins, and iii.) an elaborate regulatory network resulting in upregulation of the inhibitor of apoptosis protein (IAP) XIAP. Together, these adaptations strongly increase the threshold for apoptosis initiation when confronted with a wide range of cellular stressors. Our results highlight how human neurons are endowed with complex and redundant preemptive strategies to protect against stress and cell death.
2022-07-15 | GSE207985 | GEO
Project description:In humans, most neurons are born during embryonic development and have to persist throughout the entire lifespan of an individual. Thus, human neurons have to develop elaborate survival strategies to protect against accidental cell death. We set out to decipher the developmental adaptations resulting in neuronal resilience. We demonstrate that, during the time course of maturation, human neurons install a complex and complementary anti-apoptotic signaling network. This includes i.) a downregulation of central proteins of the intrinsic apoptosis pathway including several caspases, ii.) a shift in the ratio of pro- and anti-apoptotic BCL-2 family proteins, and iii.) an elaborate regulatory network resulting in upregulation of the inhibitor of apoptosis protein (IAP) XIAP. Together, these adaptations strongly increase the threshold for apoptosis initiation when confronted with a wide range of cellular stressors. Our results highlight how human neurons are endowed with complex and redundant preemptive strategies to protect against stress and cell death.
2022-07-15 | GSE207984 | GEO
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Project description:This SuperSeries is composed of the SubSeries listed below.
2022-07-15 | GSE207986 | GEO
Project description:Visual cortical circuits show profound plasticity during early life and are later stabilized by molecular "brakes" limiting excessive rewiring beyond a critical period. The mechanisms coordinating the expression of these factors during the transition from development to adulthood remain unknown. We found that miR-29a expression in the visual cortex dramatically increases with age, but it is not experience-dependent. Precocious high levels of miR-29a blocked ocular dominance plasticity and caused an early appearance of perineuronal nets. Conversely, inhibition of miR-29a in adult mice using LNA antagomirs activated ocular dominance plasticity, reduced perineuronal nets and restored their juvenile chemical composition. Activated adult plasticity had the typical functional and proteomic signature of critical period plasticity. Transcriptomic and proteomic studies indicated that miR-29a manipulation regulates the expression of plasticity brakes mainly affecting parvalbumin-positive interneurons. These data indicate that miR29a is a master regulator of the plasticity brakes promoting age-dependent stabilization of visual cortical circuits.
2020-11-03 | GSE141734 | GEO
Project description:Visual cortical circuits show profound plasticity during early life and are later stabilized by molecular "brakes" limiting excessive circuit rewiring beyond a critical period. How the appearance of these factors is coordinated during the transition from development to adulthood remains unknown. We analyzed the role of miR-29a, a miRNA targeting factors involved in several important pathways for plasticity such as extracellular matrix and chromatin regulation. We found that visual cortical miR-29a expression in the visual cortex dramatically increases with age, but it is not experience-dependent. Precocious high levels of miR-29a induced by targeted intracortical injections of a miR-29a mimic blocked ocular dominance plasticity and caused an early appearance of perineuronal nets. Conversely, inhibition of miR-29a in adult mice using LNA antagomirs activated ocular dominance plasticity, reduced perineuronal net intensity and number, and changed their chemical composition restoring permissive low chondroitin 4-O-sulfation levels characteristic of juvenile mice. Activated adult plasticity had the typical functional and proteomic signature of juvenile plasticity. Transcriptomic and proteomic studies indicated that miR-29a manipulation regulates the expression of plasticity factors acting at different cellular levels, from chromatin regulation to synaptic organization and extracellular matrix remodeling. Intriguingly, the projection of miR-29a regulated gene dataset onto cell-specific transcriptomes revealed that parvalbumin-positive interneurons and oligodendrocytes were the most affected cells. Overall, miR29a is a master regulator of the age-dependent plasticity brakes promoting stability of visual cortical circuits.
2020-11-04 | PXD016358 | Pride
Project description:Visual cortical circuits show profound plasticity during early life and are later stabilized by molecular "brakes" limiting excessive circuit rewiring beyond a critical period. How the appearance of these factors is coordinated during the transition from development to adulthood remains unknown. We analyzed the role of miR-29a, a miRNA targeting factors involved in several important pathways for plasticity such as extracellular matrix and chromatin regulation. We found that visual cortical miR-29a expression in the visual cortex dramatically increases with age, but it is not experience-dependent. Precocious high levels of miR-29a induced by targeted intracortical injections of a miR-29a mimic blocked ocular dominance plasticity and caused an early appearance of perineuronal nets. Conversely, inhibition of miR-29a in adult mice using LNA antagomirs activated ocular dominance plasticity, reduced perineuronal net intensity and number, and changed their chemical composition restoring permissive low chondroitin 4-O-sulfation levels characteristic of juvenile mice. Activated adult plasticity had the typical functional and proteomic signature of juvenile plasticity. Transcriptomic and proteomic studies indicated that miR-29a manipulation regulates the expression of plasticity factors acting at different cellular levels, from chromatin regulation to synaptic organization and extracellular matrix remodeling. Intriguingly, the projection of miR-29a regulated gene dataset onto cell-specific transcriptomes revealed that parvalbumin-positive interneurons and oligodendrocytes were the most affected cells. Overall, miR29a is a master regulator of the age-dependent plasticity brakes promoting stability of visual cortical circuits.
2020-11-04 | PXD016430 | Pride
Project description:Metabolic-associated steatohepatitis is a progressive fatty liver disease caused, in part, by hepatocyte stress linked to cholesterol overload. Counteracting this stress may be beneficial but there is insufficient understanding of underlying stress defenses to develop a therapeutic strategy. Here, we aimed to elucidate how stress-adaptive transcription factors, nuclear factor erythroid 2 related factor-1 (NRF1) and -2 (NRF2), counteract hepatic cholesterol overload and determine whether they function cooperatively. C57bl/6 mice were fed high fat, fructose, and cholesterol diet (HFFC). Expression profiling and phenotypic analyses were done on liver of mice with adult-onset and hepatocyte-specific deficiency of NRF1, NRF2, or both, and results compared to control. Chromatin immunoprecipitation (ChIP) sequencing was done and combined with expression profiles to identify genes that NRF1 and NRF2 interact with and regulate in vivo. Three weeks HFFC diet feeding to mice with NRF1 and NRF2 deficiency caused severe steatohepatitis and increased hepatic cholesterol storage. These outcomes did not occur in single gene-deficient mice or control. Expression profiling at a time preceding hepatic cholesterol overload and ChIP sequencing profiling revealed complementary gene regulation by NRF1 and NRF2 to promote cholesterol excretion and mitigate hazardous metabolic biproducts generated from converting cholesterol to bile acid. Consequently, combined gene deficiency, and not single-gene deficiency, increased liver oxidized protein level, decreased cholesterol in bile, and increased unconjugated bile acid in liver and bile. We discover, for the first time, that NRF1 and NRF2 work together to protect liver against damaging effects of excess cholesterol. Targeting these combined actions may prove an effective therapeutic strategy
2023-03-22 | PXD032069 | Pride