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

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

PROVIDER: PRJNA1050596 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27161307.fastq.gz	Fastqsanger.gz
	SRR27161308.fastq.gz	Fastqsanger.gz
	SRR27161309.fastq.gz	Fastqsanger.gz
	SRR27161310.fastq.gz	Fastqsanger.gz
	SRR27161311.fastq.gz	Fastqsanger.gz

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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]

| PRJNA1050599 | ENA

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

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

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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)

2024-07-19 | GSE249795 | GEO

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

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

2024-07-19 | GSE249796 | GEO

Early born neurons are abnormally positioned in the doublecortin knockout hippocampus

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

2016-10-31 | GSE87019 | GEO

Heterogeneous fates of simultaneously-born neurons during early corticogenesis

Project description:We labelled isochronic cohorts of mouse cortical neurons and analyzed their contribution to the diversity of cortical neurons. We find that early born neurons contribute to a large diversity of cortical neuron subtypes, asa also confirmed by the transcsriptomic analysis of E13.5 born neurons through Patchseq. Ultimately we identify eaarly differentiation of early born neurons as the instance characterized by the highest tranascriptomical variability which intermingles deep layer identity genes with upper layer specific ones.

2022-12-18 | GSE142601 | GEO

Single cell RNAseq of mouse olfactory bulb reveals cellular heterogeneity and activity dependent molecular census of adult-born neurons

Project description:Cellular heterogeneity within the mammalian brain poses a challenge towards understanding its complex functions. Within the olfactory bulb (OB), odor information is processed by subtypes of inhibitory interneurons whose heterogeneity and functionality is influenced by ongoing adult neurogenesis. To investigate this cellular heterogeneity, and to better understand the developmental programs of adult-born neurons, we utilized single cell RNA sequencing and computational modeling to reveal diverse and transcriptionally distinct neuronal and non-neuronal cell types. We also analyzed molecular changes during adult-born interneuron maturation, and uncovered developmental programs within their gene expression profiles. Finally, we discovered that distinct neuronal subtypes are differentially affected by sensory experience. Together, these data provide a transcriptome-based foundation for investigating subtype-specific neuronal function in the OB, charting the molecular profiles that arise during the maturation and integration of adult-born neurons, and documenting activity-dependent changes in the cellular composition of the olfactory system.

2018-12-04 | GSE121891 | GEO

Endogenous signaling through alpha7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus.

Project description:Neurogenesis in the dentate gyrus occurs throughout adult mammalian life and is essential for proper hippocampal function. Early in their development, adult-born neurons express homomeric alpha7-containing nicotinic acetylcholine receptors (alpha7-nAChRs) and receive direct cholinergic innervation. We show here that functional alpha7-nAChRs are necessary for normal survival, maturation, and integration of adult-born neurons in the dentate gyrus. Stereotaxic retroviral injection into the dentate gyrus of wild-type and alpha7-knock-out (alpha7KO) male and female mice was used to label and birthdate adult-born neurons for morphological and electrophysiological measures; BrdU (5-bromo-2-deoxyuridine) injections were used to quantify cell survival. In alpha7KO mice, we find that adult-born neurons develop with truncated, less complex dendritic arbors and display GABAergic postsynaptic currents with immature kinetics. The neurons also have a prolonged period of GABAergic depolarization characteristic of an immature state. In this condition, they receive fewer spontaneous synaptic currents and are more prone to die during the critical period when adult-born neurons are normally integrated into behaviorally relevant networks. Even those adult-born neurons that survive the critical period retain long-term dendritic abnormalities in alpha7KO mice. Interestingly, local infection with retroviral constructs to knockdown alpha7-mRNA mimics the alpha7KO phenotype, demonstrating that the relevant alpha7-nAChR signaling is cell autonomous. The results indicate a profound role for alpha7-nAChRs in adult neurogenesis and predict that alpha7-nAChR loss will cause progressive impairment in hippocampal circuitry and function over time as fewer neurons are added to the dentate gyrus and those that are added integrate less well.

| S-EPMC2905643 | biostudies-literature

Heterogeneous fates of simultaneously-born neurons in the cortical ventricular zone

Project description:Neocortical excitatory neurons belong to diverse cell types, which can be distinguished by their dates of birth, laminar location, connectivity and molecular identities. During embryogenesis, apical progenitors (APs) located in the ventricular zone first give birth to deep-layer neurons, and next to superficial-layer neurons. While the overall sequential construction of neocortical layers is well-established, whether multiple neuron types are produced by APs at single time points of corticogenesis is unknown. To address this question, here we used FlashTag to fate-map simultaneously-born (i.e. isochronic) cohorts of AP-born neurons at successive stages of corticogenesis. We reveal that early in corticogenesis, isochronic neurons differentiate into heterogeneous laminar, hodological and molecular cell types. Later on, instead, simultaneously-born neurons have more homogeneous fates. Using single-cell gene expression analyses, we identify an early postmitotic surge in the molecular heterogeneity of nascent neurons during which some early-born neurons initiate and partially execute late-born neuron transcriptional programs. Together, these findings suggest that as corticogenesis unfolds, mechanisms allowing increased homogeneity in neuronal output are progressively implemented, resulting in progressively more predictable neuronal identities.

2022-04-20 | GSE191205 | GEO

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