Characterization of ribosome heterogeneity during endothelial to hematopoietic transition

FEBS Open Bio. 2025 Jun 30. doi: 10.1002/2211-5463.70078. Online ahead of print.

Abstract

Emerging evidence has demonstrated that ribosomes are not homogeneous structures with non-specialized functions. There are now several reports of heterogeneity in the composition and functional specialization of ribosomes. Ribosome heterogeneity functions in regulating the translation of specific mRNAs, and thus plays important roles in embryonic development. However, the panorama of ribosome heterogeneity during embryonic hematopoiesis has not yet been portrayed. Here, by leveraging our single-cell transcriptomic data and a published proteomic dataset, we depict the landscape of ribosomal heterogeneity during endothelial-to-hematopoietic transition (EHT). By precisely distinguishing the different ribosomal components, we found their number and expression levels showed dynamic changes during EHT. We also report stage-specific signatures of ribosomal components. For example, RPL27 and RACK1 exhibited up-regulated expression both in dual-omics analysis and immunofluorescence experiments during EHT. Interestingly, further spatial structure analysis revealed that RACK1 localized at the bottom of 40S small ribosomal subunit, indicating its potential role in regulating ribosome function. Taken together, our study not only highlights the ribosome heterogeneity during EHT, but also provides new clues to explore how these heterogeneous machineries regulate mRNA translation.

Keywords: definitive hematopoiesis; endothelial to hematopoietic transition; mRNA translation; ribosome heterogeneity.