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<p>Neural crest cells contribute to craniofacial formation by differentiating into skeletogenic mesenchyme and neuro-glial lineages. Using Smart-seq2 single-cell transcriptomics, we show that mesenchymal fate commitment correlates specifically with the expression of rRNA-modifying and ribosome assembly factors, rather than structural ribosomal proteins. Notably, EMG1 and NHP2 introduce key post-transcriptional modifications into 18S rRNA, including m¹acp³ψ at U1248, which requires TSR3 for final maturation. Disrupting NHP2 or TSR3 in vitro and in vivo perturbs cranial neural crest differentiation; post-migratory temporal knockout of <i>Polr1a</i> or <i>Polr1c</i> also causes craniofacial malformations. These findings align with cell type-specific m¹acp³ψ levels during neural crest differentiation. Given the neural crest contribution to neuroblastoma, we analyze patient data to find that elevated ribosomal control and rRNA-modifying proteins predict poorer outcomes. Complementary experiments in neuroblastoma cell lines reveal functional roles for TSR3 and WDR74 in mesenchymal-like tumor states. Together, our results link rRNA modifications and ribosome assembly to fate decisions, suggesting ribosomal heterogeneity shapes both normal development and tumor progression.</p>

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Ribosomal modifications are associated with mesenchymal fate selection in the neural crest lineage

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月9日

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  • Irina Poverennaya,
  • Aliia Murtazina,
  • Lei Li,
  • Lorena Maili,
  • Lukas Sourada,
  • Luis Fernando Montano-Gutierrez,
  • Rozalina Galimullina,
  • Tobias Steinschaden,
  • Marketa Kaiser,
  • Tomas Zikmund,
  • Adna Goralija,
  • Teng Gao,
  • Aurore Attina,
  • Ornella Clara,
  • Christoph Bartenhagen,
  • Alek Erickson,
  • Yaakov Gershtein,
  • Shiyuan Chen,
  • Kristyna Polaskova,
  • Jaroslav Sterba,
  • Bettina Semasch,
  • Emma R. Anderson,
  • Varsha Prakash,
  • Theresa Vincent,
  • Maria Arceo,
  • Per Kogner,
  • Susanne Schlisio,
  • Peter V. Kharchenko,
  • Alexandre David,
  • Jozef Kaiser,
  • Matthias Fischer,
  • Jan Skoda,
  • Paul A. Trainor,
  • Andrei S. Chagin,
  • Igor Adameyko

摘要

Neural crest cells contribute to craniofacial formation by differentiating into skeletogenic mesenchyme and neuro-glial lineages. Using Smart-seq2 single-cell transcriptomics, we show that mesenchymal fate commitment correlates specifically with the expression of rRNA-modifying and ribosome assembly factors, rather than structural ribosomal proteins. Notably, EMG1 and NHP2 introduce key post-transcriptional modifications into 18S rRNA, including m¹acp³ψ at U1248, which requires TSR3 for final maturation. Disrupting NHP2 or TSR3 in vitro and in vivo perturbs cranial neural crest differentiation; post-migratory temporal knockout of Polr1a or Polr1c also causes craniofacial malformations. These findings align with cell type-specific m¹acp³ψ levels during neural crest differentiation. Given the neural crest contribution to neuroblastoma, we analyze patient data to find that elevated ribosomal control and rRNA-modifying proteins predict poorer outcomes. Complementary experiments in neuroblastoma cell lines reveal functional roles for TSR3 and WDR74 in mesenchymal-like tumor states. Together, our results link rRNA modifications and ribosome assembly to fate decisions, suggesting ribosomal heterogeneity shapes both normal development and tumor progression.