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The differences in local translatome across distinct neuron types is mediated by both baseline cellular differences and post-transcriptional mechanisms

ABSTRACT: The differences in local translatome across distinct neuron types is mediated by both baseline cellular differences and post-transcriptional mechanisms

PROVIDER: PRJNA495912 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8040250.fastq.gz	Fastqsanger.gz
	SRR8040260.fastq.gz	Fastqsanger.gz
	SRR8040270.fastq.gz	Fastqsanger.gz
	SRR8040280.fastq.gz	Fastqsanger.gz
	SRR8040290.fastq.gz	Fastqsanger.gz

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The differences in local translatome across distinct neuron types is mediated by both baseline cellular differences and post-transcriptional mechanisms

Project description:Local translation in neurites is a phenomenon that enhances spatial segregation of proteins and their functions away from the cell body, yet it is unclear how local translation varies across neuronal cell types. Further, it is unclear if differences in local translation across cell types simply reflect differences in transcription or if there is also a cell type specific posttranscriptional regulation of the location and translation of specific mRNAs. Most of the mRNAs discovered as locally translated have been identified from hippocampal neurons because their laminar organization facilitates neurite specific dissection and microscopy methods. Given the diversity of neurons across the brain, studies have not yet analyzed how locally translated mRNAs differ across cell types, particularly those with neurites intertwined into other cell types. Here, we used the SynapTRAP method to harvest two broad cell types in the forebrain: GABAergic neurons and pyramidal neurons. While some transcripts overlap, the majority of the local translatome is not shared across these cell types. While most differences are driven by baseline expression levels in the respective cells, some transcripts also evidence cell type specific post transcriptional regulation of localization. Finally, we provide evidence that GABAergic neurons specifically localize mRNAs for peptide neurotransmitters, including somatostatin and cortistatin, suggesting localized production of these key signaling molecules in the neurites of GABAergic neurons. Overall, this work suggests that differences in local translation in neurites across neuronal cell types are poised to contribute substantially to the variability between cells.

2018-10-12 | GSE121162 | GEO

The Differences in Local Translatome across Distinct Neuron Types Is Mediated by Both Baseline Cellular Differences and Post-transcriptional Mechanisms.

Project description:Local translation in neurites is a phenomenon that enhances the spatial segregation of proteins and their functions away from the cell body, yet it is unclear how local translation varies across neuronal cell types. Further, it is unclear whether differences in local translation across cell types simply reflect differences in transcription or whether there is also a cell type-specific post-transcriptional regulation of the location and translation of specific mRNAs. Most of the mRNAs discovered as being locally translated have been identified from hippocampal neurons because their laminar organization facilitates neurite-specific dissection and microscopy methods. Given the diversity of neurons across the brain, studies have not yet analyzed how locally translated mRNAs differ across cell types. Here, we used the SynapTRAP method to harvest two broad cell types in the mouse forebrain: GABAergic neurons and layer 5 projection neurons. While some transcripts overlap, the majority of the local translatome is not shared across these cell types. In addition to differences driven by baseline expression levels, some transcripts also exhibit cell type-specific post-transcriptional regulation. Finally, we provide evidence that GABAergic neurons specifically localize mRNAs for peptide neurotransmitters, including somatostatin and cortistatin, suggesting localized production of these key signaling molecules in the neurites of GABAergic neurons. Overall, this work suggests that differences in local translation in neurites across neuronal cell types are poised to contribute substantially to the heterogeneity in neuronal phenotypes.

| S-EPMC6361723 | biostudies-literature

Pro-opiomelanocortin (POMC) neuron translatome signatures underlying obesogenic gestational malprogramming

Project description:Maternal unbalanced nutritional habits during embryo development and perinatal stages perturb hypothalamic neuronal programming of the offspring, thus increasing “diabesity” risk. Here we report that exposure to high-fat diet during gestation and lactation did not interfere with progeny’s hypothalamic POMC neuron specification, but significantly impaired their spatial distribution and axonal extension to target areas. Importantly, we established POMC neuron-specific translatome signatures accounting for neuronal aberrant development and axonal growth. These anatomical and molecular alterations caused metabolic dysfunction in early-life and adulthood. Our study provides fundamental insights on the molecular mechanisms underlying POMC neuron malprogramming in obesogenic contexts.

2020-02-20 | GSE135639 | GEO

Pro-opiomelanocortin (POMC) neuron translatome signatures underlying obesogenic gestational malprogramming

Project description:Pro-opiomelanocortin (POMC) neuron translatome signatures underlying obesogenic gestational malprogramming

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Individual differences in stereotypy and neuron subtype translatome with TrkB deletion.

Project description:Motor stereotypies occurring in early-onset neuropsychiatric diseases are associated with dysregulated basal ganglia direct-pathway activity. Disruptions in network connectivity through impaired neuronal structure have been implicated in both rodents and humans. However, the neurobiological mechanisms leading to direct-pathway neuron disconnectivity in stereotypy remain poorly understood. We have a mouse line with Tropomyosin receptor kinase B (TrkB) receptor deletion from D1-expressing cells (D1-Cre-flTrkB) in which a subset of animals shows repetitive rotations and head tics with juvenile onset. Here we demonstrate these behaviors may be associated with abnormal direct-pathway activity by reducing rotations using chemogenetic inhibition of dorsal striatum D1-medium spiny neurons (D1-MSNs) in both juvenile and young-adult mice. Taking advantage of phenotypical differences in animals with similar genotypes, we then interrogated the D1-MSN specific translatome associated with repetitive behavior by using RNA sequencing of ribosome-associated mRNA. Detailed translatome analysis followed by multiplexed gene expression assessment revealed profound alterations in neuronal projection and synaptic structure related genes in stereotypy mice. Examination of neuronal morphology demonstrated dendritic atrophy and dendritic spine loss in dorsal striatum D1-MSNs from mice with repetitive behavior. Together, our results uncover phenotype-specific molecular alterations in D1-MSNs that relate to morphological adaptations in mice displaying stereotypy behavior.

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Protein local synthesis at synapse is required for neuromuscular transmission

Project description:To profile the local translatome at the neuromuscular junction during various developmental stages We conducted RNA sequencing of synapse-enriched regions in the mouse diaphragms of both cre- and cre+ mice to investigate the local translatome at motor neuron terminals

2024-08-26 | GSE238144 | GEO

Sex differences in the developmental patterns of the cortical astroglial cell translatome

Project description:Employing translating ribosome affinity purification with RNA sequencing (TRAPseq) on cortical tissue to isolate astroglial-specific translatome from Aldh1l1-L10-GFP mice and examine sex (male + female) and age (postnatal days 1, 4, 7, 14, 35; adults (9 weeks)) dependent changes in the astroglial translatome.

2022-02-01 | GSE192490 | GEO

Sex differences in the developmental patterns of the cortical astroglial cell translatome

Project description:Sex differences in the developmental patterns of the cortical astroglial cell translatome

| PRJNA791650 | ENA

Sex differences in the ventral tegmental area and nucleus accumbens proteome at baseline and following nicotine exposure

Project description:Sex differences in behaviors relevant to nicotine addiction have been observed in rodent models and human subjects. Behavioral, imaging and epidemiological studies also suggest underlying sex differences in mesolimbic dopamine signaling pathways. In this study we evaluated the proteome in the ventral tegmental area (VTA) and nucleus accumbens (NAc) shell in male and female mice. Experimental groups included two mouse strains (C3H/HeJ and C57BL/6J) at baseline, a sub-chronic, rewarding regimen of nicotine in C3H/HeJ mice, and chronic nicotine administration and withdrawal in C57BL/6J mice. Isobaric labeling with a TMT 10-plex system, sample fractionation, and tandem mass spectrometry were used to quantify changes in protein abundance. Similar or greater numbers of differentially regulated proteins were found between sexes at baseline in C3H/HeJ or C57BL/6J mice than within sexes following their respective regimen of nicotine administration. Despite differences by sex, strain, and nicotine exposure parameters, glial fibrillary acidic protein (GFAP) and dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32, Ppp1r1b) were repeatedly identified as significantly altered proteins, especially in the VTA. Further, network analyses showed sex- and nicotine-dependent regulation of a number of signaling pathways, including dopaminergic signaling. Sub-chronic nicotine exposure in female mice increased proteins related to dopaminergic signaling in the NAc shell but decreased them in the VTA, whereas the opposite pattern was observed in male mice. In contrast, dopaminergic signaling pathways were similarly upregulated in both male and female VTA after chronic nicotine and withdrawal. Overall, this study identifies significant sex differences in the proteome of the mesolimbic system, at baseline and after nicotine reward or withdrawal, which may help explain differential trajectories and susceptibility to nicotine addiction in males and females.

2021-06-28 | PXD023859 | Pride

Transcriptome and Translatome Profiling of Caco-2 cells

Project description:This experiment performed RNA-seq of transcriptome and translatome (translating mRNA) of Caco-2 cells We extracted transcriptome and translatome from Caco-2 cells and deep sequenced them

2014-02-18 | E-GEOD-48603 | biostudies-arrayexpress

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