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A stem cell roadmap of ribosome heterogeneity reveals a function for RPL10A in mesoderm production

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE177520 | GEO | 2022/08/31

REPOSITORIES: GEO

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Heterogeneous ribosomes exist and selectively translate distinct subpools of mRNAs in stem cells

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A stem cell roadmap of ribosome heterogeneity reveals a function for RPL10A in mesoderm production

Project description:A stem cell roadmap of ribosome heterogeneity reveals a function for RPL10A in mesoderm production

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Pervasive changes of mRNA splicing in upf1 deficient zebrafish identify rpl10a as a regulator of T cell development

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Stk40 deletion enhances c-Jun protein stability and compromises mesoderm differentiation

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