| First Author | Capron C | Year | 2011 |
| Journal | Exp Hematol | Volume | 39 |
| Issue | 6 | Pages | 629-42 |
| PubMed ID | 21420467 | Mgi Jnum | J:186954 |
| Mgi Id | MGI:5433817 | Doi | 10.1016/j.exphem.2011.02.014 |
| Citation | Capron C, et al. (2011) LYL-1 deficiency induces a stress erythropoiesis. Exp Hematol 39(6):629-42 |
| abstractText | 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. |
