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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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			Action	DRS
	SRR17873842_1.fastq.gz	Fastqsanger.gz
	SRR17873842_2.fastq.gz	Fastqsanger.gz
	SRR17873843_1.fastq.gz	Fastqsanger.gz
	SRR17873843_2.fastq.gz	Fastqsanger.gz
	SRR17875543_1.fastq.gz	Fastqsanger.gz

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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

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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

An epigenetic barrier sets the timing of human neuronal maturation.

Project description:The pace of human brain development is highly protracted compared with most other species1-7. The maturation of cortical neurons is particularly slow, taking months to years to develop adult functions3-5. Remarkably, such protracted timing is retained in cortical neurons derived from human pluripotent stem cells (hPSCs) during in vitro differentiation or upon transplantation into the mouse brain4,8,9. Those findings suggest the presence of a cell-intrinsic clock setting the pace of neuronal maturation, although the molecular nature of this clock remains unknown. Here we identify an epigenetic developmental programme that sets the timing of human neuronal maturation. First, we developed a hPSC-based approach to synchronize the birth of cortical neurons in vitro which enabled us to define an atlas of morphological, functional and molecular maturation. We observed a slow unfolding of maturation programmes, limited by the retention of specific epigenetic factors. Loss of function of several of those factors in cortical neurons enables precocious maturation. Transient inhibition of EZH2, EHMT1 and EHMT2 or DOT1L, at progenitor stage primes newly born neurons to rapidly acquire mature properties upon differentiation. Thus our findings reveal that the rate at which human neurons mature is set well before neurogenesis through the establishment of an epigenetic barrier in progenitor cells. Mechanistically, this barrier holds transcriptional maturation programmes in a poised state that is gradually released to ensure the prolonged timeline of human cortical neuron maturation.

| S-EPMC10881400 | biostudies-literature

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