A stem cell roadmap of ribosome heterogeneity reveals a function for RPL10A in mesoderm production
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PROVIDER: PRJNA737119 | ENA |
REPOSITORIES: ENA
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Project description:Recent findings suggest that the ribosome itself modulates gene expression. However, whether ribosomes change composition across cell types or control cell fate remains unknown. Here, employing quantitative mass spectrometry during human embryonic stem cell differentiation, we identify dozens of ribosome composition changes underlying cell fate specification. We observe upregulation of RPL10A/uL1-containing ribosomes in the primitive streak followed by progressive decreases during mesoderm differentiation. An Rpl10a loss-of-function allele in mice causes striking early mesodermal phenotypes, including posterior trunk truncations, and inhibits paraxial mesoderm production in culture. Ribosome profiling in Rpl10a loss-of-function mice reveals decreased translation of mesoderm regulators, including Wnt pathway mRNAs, which are also enriched on RPL10A/uL1-containing ribosomes. We further show that RPL10A/uL1 regulates canonical and non-canonical Wnt signaling during stem cell differentiation and in the developing embryo. These findings reveal unexpected ribosome composition modularity that controls differentiation and development through the specialized translation of key signaling networks.
2022-08-31 | GSE177520 | GEO
Project description:Recent findings suggest that the ribosome itself modulates gene expression. However, whether ribosomes change composition across cell types to control cell fate remains unknown. To determine the magnitude of ribosome heterogeneity and its functional contribution to cell fate specification, we measured ribosomal protein abundance in actively translating ribosomes by quantitative mass spectrometry on a day-by-day basis as human embryonic stem cells differentiate in a step-wise fashion down endoderm and mesoderm lineages. We identified numerous core ribosomal proteins (RPs) as changing significantly in abundance in actively translating ribosomes during cell fate specification, including progressive decreases in ribosome incorporation for several ribosomal proteins during mesoderm differentiation. We further traced ribosome composition changes at the cytoplasmic, whole-cell, and mRNA transcript levels and identified multiple mechanisms regulating actively translating ribosome composition. These findings reveal extensive ribosomal remodeling during differentiation, suggesting that individual ribosomal components may have cell type-specific specialized translation functions.
2022-09-19 | PXD032904 | Pride
Project description:Recent findings suggest that the ribosome itself modulates gene expression. However, whether ribosomes change composition across cell types or control cell fate remains unknown. Here, employing quantitative mass spectrometry during human embryonic stem cell differentiation, we identify dozens of ribosome composition changes underlying cell fate specification. We observe upregulation of RPL10A/uL1-containing ribosomes in the primitive streak followed by progressive decreases during mesoderm differentiation. An Rpl10a loss-of-function allele in mice causes striking early mesodermal phenotypes, including posterior trunk truncations, and inhibits paraxial mesoderm production in culture. Ribosome profiling in Rpl10a loss-of-function mice reveals decreased translation of mesoderm regulators, including Wnt pathway mRNAs, which are also enriched on RPL10A/uL1-containing ribosomes. We further show that RPL10A/uL1 regulates canonical and non-canonical Wnt signaling during stem cell differentiation and in the developing embryo. These findings reveal unexpected ribosome composition modularity that controls differentiation and development through the specialized translation of key signaling networks.
| S-EPMC9485161 | biostudies-literature
Project description:SUM159PT cells were grown either in vitro (in culture) or in vivo (mouse), after which RPL10a tagged with GFP was used to perform extraction by immoprecipitation and subsequent ribosome profiling Two batches of in vitro grown cells, each having 2 replicates. Two batches of in vivo grown cells from tumors grown in two individual mice, each having tumors on left (first batch) and right side (second batch). Extraction and ribosome profiling was done independently for the two batches of samples.
2016-02-17 | E-GEOD-74512 | biostudies-arrayexpress
Project description:Ribosomes have long been thought of as homogeneous macromolecular machines, but recent evidence suggests they are heterogeneous and could be specialised to regulate translation. Here, we have isolated ribosomal complexes and characterised their protein content across 4 tissues of Drosophila melanogaster via TMT-MS. We find that testes and ovaries contain the most heterogeneous ribosome populations, which occurs through a combination of ribosomal protein paralog-enrichment and ribosomal protein paralog-switching. We have also solved structures of ribosomes isolated from tissues by cryo-EM, revealing differences in precise ribosomal arrangement for testis and ovary 80S ribosomes. Differences in the amino acid composition of paralog pairs and their localisation on the ribosome exterior indicate paralog-switching could alter the ribosome surface, enabling different proteins to regulate translation. One testis-specific paralog-switching pair is also found in humans, suggesting this is a conserved site of ribosome heterogeneity. Overall, this work allows us to propose that mRNA translation might be regulated in the gonads through ribosome heterogeneity, providing a potential means of ribosome specialisation.
2021-07-22 | PXD026227 | Pride
Project description:SUM159PT cells were grown either in vitro (in culture) or in vivo (mouse), after which RPL10a tagged with GFP was used to perform extraction by immoprecipitation and subsequent ribosome profiling
2016-02-17 | GSE74512 | GEO
Project description:Emerging studies have linked the ribosome to more selective control of gene regulation. However, an outstanding question is whether ribosome heterogeneity at the level of core ribosomal proteins (RPs) enables ribosomes to preferentially translate specific mRNAs genome-wide. Here, we measured the absolute abundance of RPs in translating ribosomes and profiled transcripts that are enriched or depleted from select subsets of ribosomes within embryonic stem cells. We find that heterogeneity in RP composition endows ribosomes with different selectivity for translating subpools of transcripts including those controlling metabolism, the cell cycle, and development. As a paradigm example, we show that mRNAs enriched in binding to RPL10A/uL1-containing ribosomes require RPL10A/uL1 for their efficient translation. Within several of these transcripts, we find this level of regulation is mediated, at least in part, by internal ribosome entry sites. Together, these results reveal a critical functional link between ribosome heterogeneity and the post-transcriptional circuitry of gene expression.
2017-06-15 | GSE73357 | GEO
Project description:Roadmap Epigenomics Program - UCSF
| PRJNA259584 | ENA
Project description:Roadmap Epigenomics Program - Broad
| PRJNA233641 | ENA
Project description:BAC array purification of hippocampus astroglial ribosome-bound transcriptome in astrocytes from Aldh1l1:Rpl10a eGFP/ Cx43 KO and Aldh1l1:Rpl10a eGFP/ Cx43FL mice
2019-05-22 | GSE110721 | GEO