Ribosomal modifications are associated with mesenchymal fate selection in the neural crest lineage
Abstract
Abstract 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.
Article Details
Authors (35)
Irina Poverennaya
Aliia Murtazina
Lei Li
Lorena Maili
Lukas Sourada
Luis Fernando Montano-Gutierrez
Rozalina Galimullina
Tobias Steinschaden
Markéta Kaiser
Tomáš Zikmund
Adna Goralija
Teng Gao
Aurore Attina
Ornella Clara
Christoph Bartenhagen
Alek Erickson
Yaakov Gershtein
Shiyuan Chen
Kristyna Polaskova
Jaroslav Štěrba
Bettina Semasch
Emma R. Anderson
Varsha Prakash
Theresa Vincent
Maria Arceo
Per Kogner
Department of Women’s and Children’s Health, Karolinska Institutet
Susanne Schlisio
Department of Oncology and Pathology, Karolinska Institutet
Peter V. Kharchenko
Alexandre David
Jozef Kaiser
Matthias Fischer
Jan Skoda
Paul A. Trainor
Stowers Institute for Medical Research
Andrei S. Chagin
Centre for Bone and Arthritis Research, Institute of Medicine at the Sahlgrenska Academy, University of Gothenburg
Igor Adameyko