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

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, Kyle M. Loh and Maria Barna ()
Additional contact information
Naomi R. Genuth: Stanford University
Zhen Shi: Stanford University
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

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-33263-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33263-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-33263-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().