title: LYL-1 deficiency induces a stress erythropoiesis.
abstract: 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.
  
  
  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.
authors.affiliation: INSERM U1009, IFR 54, Institut Gustave Roussy, Villejuif, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Capron
authors.forename: Catherine
authors.initials: C
authors.lastname: Lacout
authors.forename: Yann
authors.initials: Y
authors.lastname: Lécluse
authors.forename: Orianne
authors.initials: O
authors.lastname: Wagner-Ballon
authors.forename: Anna-Lila
authors.initials: AL
authors.lastname: Kaushik
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cramer-Bordé
authors.forename: Fred
authors.initials: F
authors.lastname: Sablitzky
authors.forename: Dominique
authors.initials: D
authors.lastname: Duménil
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D004920:Erythropoiesis / Q000235:genetics*; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D009363:Neoplasm Proteins; C490130:Lyl1 protein, mouse