Publication Date:
2020-11-05
Description:
Introduction: RNA modifications are emerging as important determinants of cell identity and cell fate. Small nucleolar RNAs (snoRNA) guide pseudouridylation and 2'-O-methylation of RNA species. C/D box snoRNAs are essential for AML1/ETO-induced leukemia (Zhou et al. Nat Cell Biol 2017). Dynamics and relevance of these modifications in hematopoiesis are unknown. Here, we aimed to determine the plasticity of ribosomal 2'-O-methylation (Ribomethylome) patterns in hematopoietic cell populations and the interdependence with snoRNA expression, transcriptomics and proteomics. Methods: Healthy donors (19-86yrs) donated bone marrow and six cell populations were sorted or prepared: Hematopoietic stem/progenitor cell (HPC), Monocyte/macrophage precursor (MON), Granulocytic precursor (GRA), Erythroid precursor (ERY), Lymphocyte progenitor (LYM), and Mesenchymal stem/stromal cell (MSC). Small RNA sequencing and Ribometh-seq data were obtained for 65 and 55 samples, respectively. Data were analyzed together with accompanying RNA-seq and Mass-spec proteomics data which were available for all the specimens. Bioinformatics analyses were based on PCA, tSNE, spearman correlation, paired t-test, GSEA and ANOVA. Results: The analyses of 2'-O-methylation (Ribomethylome) in six bone marrow cell types from healthy donors revealed that ribosomal modifications occurred different during the process of hematopoietic differentiation. Among these sides, HPC and Myeloid lineage showed significant variability between different cell populations. Ribomethylome patterns differed between cell types and PCA analyses indicated that cellular identity was matched with a specific Ribomethylome pattern. Plasticity in Ribomethylomes were most evident for HPC, LYM, GRA and MON which showed high levels of 2'-O-methylation (almost 100% of rRNA methylated) whereas methylation levels in MSC cells were much lower (Spearman correlation
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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