A stem cell roadmap of ribosome heterogeneity reveals a function for RPL10A in mesoderm production.
Naomi R GenuthZhen ShiKoshi KunimotoVictoria HungAdele Francis XuCraig H KerrGerald C TiuJuan A Oses-PrietoRachel E A Salomon-ShulmanJeffrey D AxelrodAlma L BurlingameKyle M LohMaria BarnaPublished in: Nature communications (2022)
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.
Keyphrases
- cell fate
- pluripotent stem cells
- single cell
- stem cells
- gene expression
- mass spectrometry
- herpes simplex virus
- high resolution
- cell proliferation
- endothelial cells
- high fat diet induced
- dna methylation
- multiple sclerosis
- signaling pathway
- poor prognosis
- type diabetes
- liquid chromatography
- adipose tissue
- cell therapy
- metabolic syndrome
- quality control
- skeletal muscle
- gas chromatography
- high performance liquid chromatography
- capillary electrophoresis