ESC-sEVs rejuvenate aging hippocampal NSCs by transferring SMADs to regulate the MYT1-Egln3-Sirt1 axis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA663605 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12645860_1.fastq.gz | Fastqsanger.gz | |||
| SRR12645860_2.fastq.gz | Fastqsanger.gz | |||
| SRR12645861_1.fastq.gz | Fastqsanger.gz | |||
| SRR12645861_2.fastq.gz | Fastqsanger.gz | |||
| SRR12645862_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Tissue stem cell senescence leads to stem cell exhaustion, which results in tissue homeostasis imbalance and a decline in regeneration capacity. However, whether neural stem cells (NSCs) senescence occurs and causes neurogenesis reduction during aging is unknown. In this study, mice at different ages were used to detect age-related hippocampal NSCs (H-NSCs) senescence, as well as the function and mechanism of embryonic stem cells derived small extracellular vesicles (ESC-sEVs) in rejuvenating H-NSCs senescence. We found a progressive cognitive impairment, as well as age-related H-NSCs senescence, in mice. ESC-sEVs treatment significantly alleviated H-NSCs senescence, recovered compromised self-renewal and neurogenesis capacities, and reversed cognitive impairment. Transcriptome analysis revealed that Myelin transcription factor 1 (MYT1) is downregulated in senescent H-NSCs but upregulated by ESC-sEV treatment. In addition, knockdown of MYT1 in young H-NSCs accelerated age-related phenotypes and impaired proliferation and differentiation capacities. Mechanistically, ESC-sEVs rejuvenated senescent H-NSCs partly by transferring SMAD4 and SMAD5 to activate MYT1, which downregulated Egln3, followed by activation of HIF2α, NAMPT, and Sirt1 successively. Taken together, our results indicated that H-NSCs senescence caused cellular exhaustion, neurogenesis reduction and cognitive impairment during aging, which can be reversed by ESC-sEVs. Thus, ESC-sEVs may be promising therapeutic candidates for age-related diseases.
2023-09-09 | GSE158000 | GEO
Project description:Tissue stem cell senescence leads to stem cell exhaustion, which results in tissue homeostasis imbalance and a decline in regeneration capacity. However, whether neural stem cell (NSC) senescence occurs and causes neurogenesis reduction during aging is unknown. In this study, mice at different ages were used to detect age-related hippocampal NSC (H-NSC) senescence, as well as the function and mechanism of embryonic stem cell-derived small extracellular vesicles (ESC-sEVs) in rejuvenating H-NSC senescence. We found a progressive cognitive impairment, as well as age-related H-NSC senescence, in mice. ESC-sEV treatment significantly alleviated H-NSC senescence, recovered compromised self-renewal and neurogenesis capacities, and reversed cognitive impairment. Transcriptome analysis revealed that myelin transcription factor 1 (MYT1) is downregulated in senescent H-NSCs but upregulated by ESC-sEV treatment. In addition, knockdown of MYT1 in young H-NSCs accelerated age-related phenotypes and impaired proliferation and differentiation capacities. Mechanistically, ESC-sEVs rejuvenated senescent H-NSCs partly by transferring SMAD family members 4 (SMAD4) and 5 (SMAD5) to activate MYT1, which downregulated egl-9 family hypoxia inducible factor 3 (Egln3), followed by activation of hypoxia inducible factor 2 subunit α (HIF-2α), nicotinamide phosphoribosyl transferase (NAMPT), and sirtuin 1 (Sirt1) successively. Taken together, our results indicated that H-NSC senescence caused cellular exhaustion, neurogenesis reduction, and cognitive impairment during aging, which can be reversed by ESC-sEVs. Thus, ESC-sEVs may be promising therapeutic candidates for age-related diseases.
| S-EPMC7791087 | biostudies-literature
Project description:Here we performed a ChIP-seq experiment on a sample of adherent cultures of mouse neural stem cells (NS5 cell line) expressing an inducible HA-tagged version of the proneural factor MyT1 (MyT1-HA, under TetON control) after activation by doxycycline hyclate (DOX). This resulted in the generation of a genome-wide map of MyT1-HA binding to chromatin.
2016-09-09 | E-MTAB-4330 | biostudies-arrayexpress
Project description:The current study aims were to determine the differential expression of Myo-sEVs derived from normal or HG/HL.Mouse primary myocardial cells were isolated and cultured in normal and HG/HL culture medium. Myo-sEVs were separated by ultracentrifugation.Differential myo-sEVs-miRNA expression obtained through Unbiased miRNA array analysis.
2024-02-07 | E-MTAB-13736 | biostudies-arrayexpress
Project description:Here we performed a microarray experiment on samples of adherent cultures of mouse neural stem cells (NS5 cell line) expressing an inducible version of the transcription factor MyT1 (MyT1-V5 TetON) under normal growth conditions and after 4 hours of treatment by doxycyline. This resulted in the generation of a genome-wide mRNA expression pattern and quantification for these cells in the two conditions.
2016-09-09 | E-MTAB-4335 | biostudies-arrayexpress
Project description:We report the changes in gene expression in U87 glioblastoma cells with re-introduced Myt1 or Myt1l.
2018-01-24 | GSE103790 | GEO
Project description:Members of the Myt (myelin transcription factor) family have been implicated in neuronal development. However, their in vivo roles in OL lineage development have not been systematically investigated. Here, we identified Myt1 transcription factor as a crucial regulator of oligodendrocyte differentiation in the developing central nervous system. Conventional knockout of Myt1 causes a remarkable delay in the initiation of OL differentiation, without affecting the generation and proliferation of OPCs. Conversely, hyperactivation of Myt1 induces precocious OL differentiation both in vitro and in vivo. Using a combination of RNA-seq and ChIP-seq analyses, we identified Nkx2.2 as a key target of Myt1 to switch on the OL differentiation program. Mechanistically, specific binding of Myt1 in the Nkx2.2 gene loci inhibits the nucleosomal histone deacetylation via hindering the HDAC1 repressor complex integrity and reducing the deacetylation activity of HDAC1. Additionally, we demonstrated that Myt1 functions downstream of Notch signaling pathway in controlling the timing of OL differentiation. Collectively, our data demonstrate that Myt1 is a major regulator of OL differentiation and provide insight into the epigenetic regulatory mechanisms under OL development. Myt1 is, therefore, a promising therapeutic target for enhancing the OL differentiation and myelination/remyelination during development or after demyelination insults.
2024-10-01 | GSE253491 | GEO
Project description:Members of the Myt (myelin transcription factor) family have been implicated in neuronal development. However, their in vivo roles in OL lineage development have not been systematically investigated. Here, we identified Myt1 transcription factor as a crucial regulator of oligodendrocyte differentiation in the developing central nervous system. Conventional knockout of Myt1 causes a remarkable delay in the initiation of OL differentiation, without affecting the generation and proliferation of OPCs. Conversely, hyperactivation of Myt1 induces precocious OL differentiation both in vitro and in vivo. Using a combination of RNA-seq and ChIP-seq analyses, we identified Nkx2.2 as a key target of Myt1 to switch on the OL differentiation program. Mechanistically, specific binding of Myt1 in the Nkx2.2 gene loci inhibits the nucleosomal histone deacetylation via hindering the HDAC1 repressor complex integrity and reducing the deacetylation activity of HDAC1. Additionally, we demonstrated that Myt1 functions downstream of Notch signaling pathway in controlling the timing of OL differentiation. Collectively, our data demonstrate that Myt1 is a major regulator of OL differentiation and provide insight into the epigenetic regulatory mechanisms under OL development. Myt1 is, therefore, a promising therapeutic target for enhancing the OL differentiation and myelination/remyelination during development or after demyelination insults.
2024-10-01 | GSE253256 | GEO
Project description:Members of the Myt (myelin transcription factor) family have been implicated in neuronal development. However, their in vivo roles in OL lineage development have not been systematically investigated. Here, we identified Myt1 transcription factor as a crucial regulator of oligodendrocyte differentiation in the developing central nervous system. Conventional knockout of Myt1 causes a remarkable delay in the initiation of OL differentiation, without affecting the generation and proliferation of OPCs. Conversely, hyperactivation of Myt1 induces precocious OL differentiation both in vitro and in vivo. Using a combination of RNA-seq and ChIP-seq analyses, we identified Nkx2.2 as a key target of Myt1 to switch on the OL differentiation program. Mechanistically, specific binding of Myt1 in the Nkx2.2 gene loci inhibits the nucleosomal histone deacetylation via hindering the HDAC1 repressor complex integrity and reducing the deacetylation activity of HDAC1. Additionally, we demonstrated that Myt1 functions downstream of Notch signaling pathway in controlling the timing of OL differentiation. Collectively, our data demonstrate that Myt1 is a major regulator of OL differentiation and provide insight into the epigenetic regulatory mechanisms under OL development. Myt1 is, therefore, a promising therapeutic target for enhancing the OL differentiation and myelination/remyelination during development or after demyelination insults.
2024-10-01 | GSE253254 | GEO
Project description:Members of the Myt (myelin transcription factor) family have been implicated in neuronal development. However, their in vivo roles in OL lineage development have not been systematically investigated. Here, we identified Myt1 transcription factor as a crucial regulator of oligodendrocyte differentiation in the developing central nervous system. Conventional knockout of Myt1 causes a remarkable delay in the initiation of OL differentiation, without affecting the generation and proliferation of OPCs. Conversely, hyperactivation of Myt1 induces precocious OL differentiation both in vitro and in vivo. Using a combination of RNA-seq and ChIP-seq analyses, we identified Nkx2.2 as a key target of Myt1 to switch on the OL differentiation program. Mechanistically, specific binding of Myt1 in the Nkx2.2 gene loci inhibits the nucleosomal histone deacetylation via hindering the HDAC1 repressor complex integrity and reducing the deacetylation activity of HDAC1. Additionally, we demonstrated that Myt1 functions downstream of Notch signaling pathway in controlling the timing of OL differentiation. Collectively, our data demonstrate that Myt1 is a major regulator of OL differentiation and provide insight into the epigenetic regulatory mechanisms under OL development. Myt1 is, therefore, a promising therapeutic target for enhancing the OL differentiation and myelination/remyelination during development or after demyelination insults.
2024-10-01 | GSE253255 | GEO