LYL-1 deficiency induces a stress erythropoiesis
| Autor: | Fred Sablitzky, Elisabeth Cramer-Bordé, William Vainchenker, Catherine Lacout, Orianne Wagner-Ballon, Claude Capron, Yann Lécluse, Dominique Duménil, Anna-Lila Kaushik |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Spleen Biology Flow cytometry Mice Stress Physiological hemic and lymphatic diseases Precursor cell Basic Helix-Loop-Helix Transcription Factors Genetics medicine Animals Erythropoiesis Molecular Biology Transcription factor DNA Primers Mice Knockout Base Sequence medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction Cell Biology Hematology Flow Cytometry Molecular biology Neoplasm Proteins Mice Inbred C57BL Reverse transcription polymerase chain reaction medicine.anatomical_structure Erythropoietin Immunology Bone marrow medicine.drug |
| Zdroj: | Experimental Hematology. 39:629-642 |
| ISSN: | 0301-472X |
| DOI: | 10.1016/j.exphem.2011.02.014 |
| Popis: | Objective LYL-1 is a transcription factor containing a basic helix-loop-helix motif closely related to SCL/TAL-1, a regulator of erythroid differentiation. Because LYL-1 is expressed in erythroid cell populations, we addressed its role in erythropoiesis using knockin mice. Materials and Methods Erythropoiesis of LYL-1 −/− mice was studied by progenitor assays, flow cytometry, reconstitution assays, and functional tests. Expression of LYL-1, SCL , and GATA-1 was assessed at messenger RNA level by quantitative reverse transcription polymerase chain reaction. Results LYL-1 −/− mice displayed decreased erythropoiesis with a partial arrest in differentiation, and enhanced apoptosis associated with decreased Bcl-x L expression in the bone marrow (BM). In addition, LYL-1 −/− BM cells were severely impaired in their abilities to reconstitute the erythroid lineage in competitive assays, suggesting a cell autonomous abnormality of erythropoiesis. In parallel, erythroid progenitor and precursor cells were significantly increased in the spleen of LYL-1 −/− mice. Expression of LYL-1 was differentially regulated during maturation of erythroblasts and strikingly different between spleen- and BM-derived erythroblasts. Expression of LYL-1 decreased during erythroid differentiation in the spleen whereas it increased in the BM to reach the same level in mature erythroblasts as in the soleen. Loss of Lyl-1 expression was accompanied with an increase of SCL / TAL-1 and GATA-1 transcripts in spleen but not in BM-derived erythroblasts. Furthermore, phenylhydrazine-induced stress erythropoiesis was elevated in LYL-1 −/− mice and mutant BM and spleen erythroid progenitors were hypersensitive to erythropoietin. Conclusions Taken together, these results suggest that LYL-1 plays a definite role in erythropoiesis, albeit with different effects in BM specifically regulating basal erythropoiesis, and spleen, controlling stress-induced erythropoiesis. |
| Databáze: | OpenAIRE |
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