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Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus [ds2]

ABSTRACT: Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus [ds2]

PROVIDER: PRJNA1050600 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27161341.fastq.gz	Fastqsanger.gz
	SRR27161342.fastq.gz	Fastqsanger.gz
	SRR27161343.fastq.gz	Fastqsanger.gz
	SRR27161344.fastq.gz	Fastqsanger.gz
	SRR27161345.fastq.gz	Fastqsanger.gz

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Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus

Project description:Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus

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Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus [ds1]

Project description:Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus [ds1]

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Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus [ds2]

Project description:To profile neurogenesis in the adult mouse hippocampus, we utilized a strategy to isolate developing cells derived from RGLs expressing the proneural gene Achaete-scute homolog 1 (Ascl1). Tamoxifen administration to young-adult Ascl1CreERT2;CAGfloxStopSun1sfGFP mice were used to induce the expression of Sun1-sfGFP in the nuclear membrane of RGLs and permanently label their progeny. This birthdating tag enabled a comprehensive analysis of the entire process encompassing neuronal differentiation, development, and functional maturation. This dataset was built using FACS-sorted nuclei obtained from dentate gyri microdissected at 2-, 3-, 4-, 5- and 8 weeks after TAM induction (cohorts w2 through w8)

2024-07-19 | GSE249794 | GEO

Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus [ds1]

Project description:To profile neurogenesis in the adult mouse hippocampus, we utilized a strategy to isolate developing cells derived from RGLs expressing the proneural gene Achaete-scute homolog 1 (Ascl1). Tamoxifen administration to young-adult Ascl1CreERT2;CAGfloxStopSun1sfGFP mice were used to induce the expression of Sun1-sfGFP in the nuclear membrane of RGLs and permanently label their progeny. This birthdating tag enabled a comprehensive analysis of the entire process encompassing neuronal differentiation, development, and functional maturation. This dataset was built using FACS-sorted nuclei obtained from dentate gyri microdissected at 1-, 2-, 4-, and 8 weeks after TAM induction (cohorts w1 through w8)

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Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus.

Project description:The adult hippocampus generates new granule cells (aGCs) with functional capabilities that convey unique forms of plasticity to the preexisting circuits. While early differentiation of adult radial glia-like cells (RGLs) has been studied extensively, the molecular mechanisms guiding the maturation of postmitotic neurons remain unknown. Here, we used a precise birthdating strategy to study aGC differentiation using single-nuclei RNA sequencing. Transcriptional profiling revealed a continuous trajectory from RGLs to mature aGCs, with multiple immature stages bearing increasing levels of effector genes supporting growth, excitability, and synaptogenesis. Analysis of differential gene expression, pseudo-time trajectory, and transcription factors (TFs) revealed critical transitions defining four cellular states: quiescent RGLs, proliferative progenitors, immature aGCs, and mature aGCs. Becoming mature aGCs involved a transcriptional switch that shuts down pathways promoting cell growth, such SoxC TFs, to activate programs that likely control neuronal homeostasis. aGCs overexpressing Sox4 or Sox11 remained immature. Our results unveil precise molecular mechanisms driving adult RGLs through the pathway of neuronal differentiation.

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Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus

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Project description:Human doublecortin (DCX) mutations are associated with severe brain malformations leading to aberrant neuron positioning (heterotopia), intellectual disability and epilepsy. The Dcx protein plays a key role in neuronal migration, and hippocampal pyramidal neurons in Dcx knockout (KO) mice are disorganized. The single CA3 pyramidal cell layer observed in wild type (WT) is present as two abnormal layers in the KO, and CA3 KO pyramidal neurons are more excitable than WT. Dcx KO mice also exhibit spontaneous epileptic activity originating in the hippocampus. It is unknown however, how hyperexcitability arises and why two CA3 layers are observed. Transcriptome analyses were performed to search for perturbed postnatal gene expression, comparing Dcx KO CA3 pyramidal cell layers with WT. Gene expression changes common to both KO layers indicated mitochondria and Golgi apparatus anomalies, as well as increased cell stress. Intriguingly, gene expression analyses also suggested that the KO layers differ significantly from each other, particularly in terms of maturity. Layer-specific molecular markers and BrdU birthdating to mark the final positions of neurons born at distinct timepoints revealed inverted layering of the CA3 region in Dcx KO animals. Notably, many early-born ‘outer boundary’ neurons are located in an inner position in the Dcx KO CA3, superficial to other pyramidal neurons. This abnormal positioning likely affects cell morphology and connectivity, influencing network function. Dissecting this Dcx KO phenotype sheds light on coordinated developmental mechanisms of neuronal subpopulations, as well as gene expression patterns contributing to a bi-layered malformation associated with epilepsy. Expression profiling by array

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