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An epigenetic barrier in neural progenitor cells and early neurons set the timing of human neuronal maturation

ABSTRACT: An epigenetic barrier in neural progenitor cells and early neurons set the timing of human neuronal maturation

PROVIDER: PRJNA803211 | ENA |

REPOSITORIES: ENA

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An epigenetic barrier sets the timing of human neuronal maturation

Project description:An epigenetic barrier sets the timing of human neuronal maturation

| PRJNA803355 | ENA

An epigenetic barrier in neural progenitor cells and early neurons set the timing of human neuronal maturation [ATAC-seq]

Project description:A challenge for understanding the development of brain circuits is to identify the factors that instruct neurons to accomplish each developmental steps at the appropriate stage. Neuronal maturation follows an intrinsic species-specific developmental pace that is extremely protracted in humans and that is retained during human pluripotent stem cells (hPSCs) differentiations. Using a novel platform that synchronized the generation of cortical neurons from hPSC, we established morphological, functional, and molecular roadmaps of maturation. We found that the temporal unfolding of maturation programs proceeds gradually and is limited by the retention of complex epigenetic signatures. Loss-of-function of multiple such epigenetic factors at the neuron stage triggered precocious molecular and functional maturation. Remarkably, transient pharmacological manipulation of a subset of epigenetic factors, including EZH2, EHMT1/2 and DOT1L, at the progenitor cell stage can prime precursors to reach enhanced molecular and functional signatures of maturity as neurons. Our results indicate that the rate at which neurons mature is set well before neurogenesis through the establishment of an “epigenetic barrier” in progenitor cells that gets slowly erased in neurons, allowing the gradual onset of maturation programs.

2023-11-06 | GSE196074 | GEO

An epigenetic barrier in neural progenitor cells and early neurons set the timing of human neuronal maturation [RNA-seq]

2023-11-06 | GSE196073 | GEO

An epigenetic barrier in neural progenitor cells and early neurons set the timing of human neuronal maturation [ATAC-seq]

Project description:An epigenetic barrier in neural progenitor cells and early neurons set the timing of human neuronal maturation [ATAC-seq]

| PRJNA803215 | ENA

An epigenetic barrier in neural progenitor cells and early neurons set the timing of human neuronal maturation [RNA-seq]

Project description:An epigenetic barrier in neural progenitor cells and early neurons set the timing of human neuronal maturation [RNA-seq]

| PRJNA803216 | ENA

An epigenetic barrier in neural progenitor cells and early neurons sets the timing of human neuronal maturation

Project description:An epigenetic barrier in neural progenitor cells and early neurons sets the timing of human neuronal maturation

| PRJNA939185 | ENA

An epigenetic barrier sets the timing of human neuronal maturation

Project description:A challenge for understanding the development of brain circuits is to identify the factors that instruct neurons to accomplish each developmental step at the appropriate stage. Neuronal maturation follows an intrinsic species-specific developmental pace that is extremely protracted in humans and that is retained during human pluripotent stem cells (hPSCs) differentiations. Using a novel platform that synchronized the generation of cortical neurons from hPSC, we established morphological, functional, and molecular roadmaps of maturation. We found that the temporal unfolding of maturation programs proceeds gradually and is limited by the retention of complex epigenetic signatures. Loss-of-function of multiple such epigenetic factors at the neuron stage triggered precocious molecular and functional maturation. Remarkably, transient pharmacological manipulation of a subset of epigenetic factors, including EZH2, EHMT1/2 and DOT1L, at the progenitor cell stage can prime precursors to reach enhanced molecular and functional signatures of maturity as neurons. Our results indicate that the rate at which neurons mature is set well before neurogenesis through the establishment of an “epigenetic barrier” in progenitor cells that gets slowly erased in neurons, allowing the gradual onset of maturation programs.

2023-11-09 | GSE196109 | GEO

An epigenetic barrier in neural progenitor cells and early neurons sets the timing of human neuronal maturation

2023-11-06 | GSE226223 | GEO

An epigenetic barrier in neural progenitor cells and early neurons set the timing of human neuronal maturation

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

2023-11-06 | GSE196075 | GEO

Glutamatergic neuronal activity regulates retinal angiogenesis and blood-retinal barrier via Norrin/b-catenin signaling

Project description:Interactions among neuroglial and vascular components are crucial for retinal angiogenesis and blood-retinal barrier (BRB) maturation. Neuronal synaptic dysfunctions precede vascular abnormalities in many retinal pathologies. However, whether neuronal activity, specifically glutamatergic activity, regulates retinal angiogenesis and BRB maturation remains unclear. Using in vivo genetic studies in mice, single-cell RNA-sequencing and functional validation, we found that deep plexus angiogenesis and paracellular BRB maturation are delayed in Vglut1-/- retinas, where neurons fail to release glutamate. In contrast, deep plexus angiogenesis and paracellular BRB maturation are accelerated in Gnat1-/- retinas, where constitutively depolarized rods release excess glutamate. Mechanistically, Norrin expression and endothelial Norrin/b-catenin signaling are downregulated in Vglut1-/- retinas, and upregulated in Gnat1-/- retinas. Pharmacological activation of endothelial Norrin/ b-catenin signaling in Vglut1-/- retinas rescued both deep plexus angiogenesis and paracellular BRB integrity. Thus, our findings demonstrate that glutamatergic neuronal activity regulates retinal angiogenesis and BRB maturation by modulating Norrin/b-catenin signaling.

2024-06-27 | GSE235993 | GEO

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