Loss of Ribosomal Protein Paralog Rpl22-like1 Blocks Lymphoid Development without Affecting Protein Synthesis
| Autor: | Shawn P. Fahl, Robert Sertori, Yong Zhang, Alejandra V. Contreras, Bryan Harris, Minshi Wang, Jacqueline Perrigoue, Siddharth Balachandran, Brian K. Kennedy, David L. Wiest |
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| Rok vydání: | 2021 |
| Předmět: |
Mice
Knockout Ribosomal Proteins B-Lymphocytes Gene Expression Profiling Lymphopoiesis Immunology Cell Plasticity Cell Differentiation Hematopoietic Stem Cells Article Immunophenotyping Mice Protein Biosynthesis Immunology and Allergy Animals Cell Lineage Lymphocytes Tumor Suppressor Protein p53 Spleen |
| Zdroj: | J Immunol |
| ISSN: | 1550-6606 |
| Popis: | Ribosomal proteins are thought to primarily facilitate biogenesis of the ribosome and its ability to synthesize protein. However, in this study, we show that Rpl22-like1 (Rpl22l1) regulates hematopoiesis without affecting ribosome biogenesis or bulk protein synthesis. Conditional loss of murine Rpl22l1 using stage or lineage-restricted Cre drivers impairs development of several hematopoietic lineages. Specifically, Tie2-Cre–mediated ablation of Rpl22l1 in hemogenic endothelium impairs the emergence of embryonic hematopoietic stem cells. Ablation of Rpl22l1 in late fetal liver progenitors impairs the development of B lineage progenitors at the pre-B stage and development of T cells at the CD44−CD25+ double-negative stage. In vivo labeling with O-propargyl-puromycin revealed that protein synthesis at the stages of arrest was not altered, indicating that the ribosome biogenesis and function were not generally compromised. The developmental arrest was associated with p53 activation, suggesting that the arrest may be p53-dependent. Indeed, development of both B and T lymphocytes was rescued by p53 deficiency. p53 induction was not accompanied by DNA damage as indicated by phospho-γH2AX induction or endoplasmic reticulum stress, as measured by phosphorylation of EIF2α, thereby excluding the known likely p53 inducers as causal. Finally, the developmental arrest of T cells was not rescued by elimination of the Rpl22l1 paralog, Rpl22, as we had previously found for the emergence of hematopoietic stem cells. This indicates that Rpl22 and Rpl22l1 play distinct and essential roles in supporting B and T cell development. |
| Databáze: | OpenAIRE |
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