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A stem cell roadmap of ribosome heterogeneity reveals a function for RPL10A in mesoderm production.
Genuth, Naomi R; Shi, Zhen; Kunimoto, Koshi; Hung, Victoria; Xu, Adele F; Kerr, Craig H; Tiu, Gerald C; Oses-Prieto, Juan A; Salomon-Shulman, Rachel E A; Axelrod, Jeffrey D; Burlingame, Alma L; Loh, Kyle M; Barna, Maria.
Afiliación
  • Genuth NR; Department of Genetics, Stanford University, Stanford, CA, 94305, USA.
  • Shi Z; Department of Biology, Stanford University, Stanford, CA, 94305, USA.
  • Kunimoto K; Department of Genetics, Stanford University, Stanford, CA, 94305, USA.
  • Hung V; Genentech Inc, South San Francisco, CA, 94080, USA.
  • Xu AF; Department of Pathology, Stanford University, Stanford, CA, 94305, USA.
  • Kerr CH; Department of Genetics, Stanford University, Stanford, CA, 94305, USA.
  • Tiu GC; Department of Genetics, Stanford University, Stanford, CA, 94305, USA.
  • Oses-Prieto JA; Department of Genetics, Stanford University, Stanford, CA, 94305, USA.
  • Salomon-Shulman REA; Department of Genetics, Stanford University, Stanford, CA, 94305, USA.
  • Axelrod JD; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, 94158, USA.
  • Burlingame AL; Department of Developmental Biology, Stanford University, Stanford, CA, 94305, USA.
  • Loh KM; Department of Pathology, Stanford University, Stanford, CA, 94305, USA.
  • Barna M; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, 94158, USA.
Nat Commun ; 13(1): 5491, 2022 09 19.
Article en En | MEDLINE | ID: mdl-36123354
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.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Proteínas Ribosómicas / Células Madre / Mesodermo Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Proteínas Ribosómicas / Células Madre / Mesodermo Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos