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

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Listed:
  • Naomi R. Genuth

    (Stanford University
    Stanford University)

  • Zhen Shi

    (Stanford University
    Genentech Inc)

  • Koshi Kunimoto

    (Stanford University)

  • Victoria Hung

    (Stanford University)

  • Adele F. Xu

    (Stanford University)

  • Craig H. Kerr

    (Stanford University)

  • Gerald C. Tiu

    (Stanford University)

  • Juan A. Oses-Prieto

    (University of California San Francisco)

  • Rachel E. A. Salomon-Shulman

    (Stanford University)

  • Jeffrey D. Axelrod

    (Stanford University)

  • Alma L. Burlingame

    (University of California San Francisco)

  • Kyle M. Loh

    (Stanford University)

  • Maria Barna

    (Stanford University)

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.

Suggested Citation

  • Naomi R. Genuth & Zhen Shi & Koshi Kunimoto & Victoria Hung & Adele F. Xu & Craig H. Kerr & Gerald C. Tiu & Juan A. Oses-Prieto & Rachel E. A. Salomon-Shulman & Jeffrey D. Axelrod & Alma L. Burlingame, 2022. "A stem cell roadmap of ribosome heterogeneity reveals a function for RPL10A in mesoderm production," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33263-3
    DOI: 10.1038/s41467-022-33263-3
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    References listed on IDEAS

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    2. Andreas M. Anger & Jean-Paul Armache & Otto Berninghausen & Michael Habeck & Marion Subklewe & Daniel N. Wilson & Roland Beckmann, 2013. "Structures of the human and Drosophila 80S ribosome," Nature, Nature, vol. 497(7447), pages 80-85, May.
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    Cited by:

    1. Azelle Hawdon & Niall D. Geoghegan & Monika Mohenska & Anja Elsenhans & Charles Ferguson & Jose M. Polo & Robert G. Parton & Jennifer Zenker, 2023. "Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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