Similar Datasets
Project description:The brain displays the richest repertoire of post-transcriptional mechanisms regulating mRNA translation1–12. Among these, alternative isoform expression has been shown to drive cell type specificity and, when disrupted, is strongly linked to neurological disorders13–18. However, genome-wide measurements of mRNA translation with isoform-sensitivity at single-cell resolution have not been achieved. To address this, we deployed Ribo-STAMP (Surveying Ribosomal Targets by APOBEC-Mediated Profiling) coupled with short- and long-read single-cell RNA-sequencing in the brain19. We generated the first isoform-sensitive single cell translatomes of the mouse hippocampus, discovering 797 alternative isoforms across 325 genes, with CA1 exhibiting the most differentially expressed and CA3 the most differentially translated isoforms. We defined high and low translational states in CA1 and CA3 neurons, with ribosomal, metabolic, and synaptic genes enriched in high states. Surprisingly, we found that CA3 neurons exhibited higher basal translation compared to CA1, as confirmed by metabolic labeling of newly synthesized proteins and immunohistochemistry of mRNA translation factors. This easily adoptable platform will expand our understanding of how isoform-specific translation drives brain physiology and disease.
2025-12-22 | GSE276504 | GEO
Project description:The brain displays the richest repertoire of post-transcriptional mechanisms regulating mRNA translation1–12. Among these, alternative isoform expression has been shown to drive cell type specificity and, when disrupted, is strongly linked to neurological disorders13–18. However, genome-wide measurements of mRNA translation with isoform-sensitivity at single-cell resolution have not been achieved. To address this, we deployed Ribo-STAMP (Surveying Ribosomal Targets by APOBEC-Mediated Profiling) coupled with short- and long-read single-cell RNA-sequencing in the brain19. We generated the first isoform-sensitive single cell translatomes of the mouse hippocampus, discovering 797 alternative isoforms across 325 genes, with CA1 exhibiting the most differentially expressed and CA3 the most differentially translated isoforms. We defined high and low translational states in CA1 and CA3 neurons, with ribosomal, metabolic, and synaptic genes enriched in high states. Surprisingly, we found that CA3 neurons exhibited higher basal translation compared to CA1, as confirmed by metabolic labeling of newly synthesized proteins and immunohistochemistry of mRNA translation factors. This easily adoptable platform will expand our understanding of how isoform-specific translation drives brain physiology and disease.
2025-12-22 | GSE275091 | GEO
Project description:The brain displays the richest repertoire of post-transcriptional mechanisms regulating mRNA translation. Among these, alternative splicing has been shown to drive cell type specificity and, when disrupted, is strongly linked to neurological disorders. However, genome-wide measurements of mRNA translation with isoform-sensitivity at single-cell (sc) resolution have not been achieved. To address this, we deployed Ribo-STAMP (Surveying Ribosomal Targets by APOBEC-Mediated Profiling) coupled with short- and long-read scRNA-sequencing (scRNA-seq) in the brain20. We generated the first isoform-sensitive sc translatomes of the mouse hippocampus at postnatal day 25, discovering cell type-specific translation of 3,857 alternative transcripts across 1,641 genes, and identifying isoforms of the same genes undergoing differential translation within and across eight different cell types. We defined high and low translational states in CA1 and CA3 neurons, with synaptic and metabolic genes enriched in high states. Surprisingly, we found that CA3 exhibited higher basal translation compared to CA1, as confirmed by metabolic labeling of newly synthesized proteins and immunohistochemistry of translational machinery components. This accessible platform will expand our understanding of how cell type- and isoform-specific translation drives brain physiology and disease.
2025-12-22 | GSE314058 | GEO
Project description:The brain displays the richest repertoire of post-transcriptional mechanisms regulating mRNA translation1–12. Among these, alternative isoform expression has been shown to drive cell type specificity and, when disrupted, is strongly linked to neurological disorders13–18. However, genome-wide measurements of mRNA translation with isoform-sensitivity at single-cell resolution have not been achieved. To address this, we deployed Ribo-STAMP (Surveying Ribosomal Targets by APOBEC-Mediated Profiling) coupled with short- and long-read single-cell RNA-sequencing in the brain19. We generated the first isoform-sensitive single cell translatomes of the mouse hippocampus, discovering 797 alternative isoforms across 325 genes, with CA1 exhibiting the most differentially expressed and CA3 the most differentially translated isoforms. We defined high and low translational states in CA1 and CA3 neurons, with ribosomal, metabolic, and synaptic genes enriched in high states. Surprisingly, we found that CA3 neurons exhibited higher basal translation compared to CA1, as confirmed by metabolic labeling of newly synthesized proteins and immunohistochemistry of mRNA translation factors. This easily adoptable platform will expand our understanding of how isoform-specific translation drives brain physiology and disease.
2025-12-22 | GSE275133 | GEO
Project description:Single cell and isoform-specific translational profiling of the mouse brain
| PRJNA1390205 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-06-19 | E-GEOD-52451 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-02-10 | GSE163532 | GEO
Project description:The brain displays the richest repertoire of post-transcriptional mechanisms regulating mRNA translation. Among these, alternative splicing has been shown to drive cell type specificity and, when disrupted, is strongly linked to neurological disorders. However, genome-wide measurements of mRNA translation with isoform-sensitivity at single-cell (sc) resolution have not been achieved. To address this, we deployed Ribo-STAMP (Surveying Ribosomal Targets by APOBEC-Mediated Profiling) coupled with long-read scRNA-sequencing (scRNA-seq) in the brain. We generated the first isoform-sensitive sc translatomes of the mouse hippocampus at postnatal day 25, discovering cell type-specific translation of 3,857 alternative transcripts across 1,641 genes, and identifying isoforms of the same genes undergoing differential translation within and across eight different cell types. We defined high and low translational states in CA1 and CA3 neurons, with synaptic and metabolic genes enriched in high states. Surprisingly, we found that CA3 exhibited higher basal translation compared to CA1, as confirmed by metabolic labeling of newly synthesized proteins and immunohistochemistry of translational machinery components. This accessible platform will expand our understanding of how cell type- and isoform-specific translation drives brain physiology and disease.
2025-12-22 | GSE314059 | GEO
Project description:Alternative translation initiation and stop codon readthrough in a few well-studied cases have been shown to allow the same transcript to generate multiple protein variants. Because the brain shows a particularly abundant use of alternative splicing, we sought to study alternative translation in CNS cells. We show that alternative translation is widespread and regulated across brain transcripts. In neural cultures, we identify alternative initiation on hundreds of transcripts, confirm several N-terminal protein variants, and show the modulation of the phenomenon by KCl stimulation. We also detect readthrough in cultures and show differential levels of normal and readthrough versions of AQP4 in gliotic diseases. Finally, we couple translating ribosome affinity purification to ribosome footprinting (TRAP-RF) for cell-type-specific analysis of neuronal and astrocytic translational readthrough in the mouse brain. We demonstrate that this unappreciated mechanism generates numerous and diverse protein isoforms in a cell-type-specific manner in the brain.
| S-EPMC6392083 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-12-01 | E-GEOD-51740 | biostudies-arrayexpress