Your browser doesn't support javascript.
loading
Deletion of the Scl +19 enhancer increases the blood stem cell compartment without affecting the formation of mature blood lineages.
Spensberger, Dominik; Kotsopoulou, Ekaterini; Ferreira, Rita; Broccardo, Cyril; Scott, Linda M; Fourouclas, Nasios; Ottersbach, Katrin; Green, Anthony R; Göttgens, Berthold.
Afiliación
  • Spensberger D; Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Exp Hematol ; 40(7): 588-598.e1, 2012 Jul.
Article en En | MEDLINE | ID: mdl-22401818
The stem cell leukemia (Scl)/Tal1 gene is essential for normal blood and endothelial development, and is expressed in hematopoietic stem cells (HSCs), progenitors, erythroid, megakaryocytic, and mast cells. The Scl +19 enhancer is active in HSCs and progenitor cells, megakaryocytes, and mast cells, but not mature erythroid cells. Here we demonstrate that in vivo deletion of the Scl +19 enhancer (Scl(Δ19/Δ19)) results in viable mice with normal Scl expression in mature hematopoietic lineages. By contrast, Scl expression is reduced in the stem/progenitor compartment and flow cytometry analysis revealed that the HSC and megakaryocyte-erythroid progenitor populations are enlarged in Scl(Δ19/Δ19) mice. The increase in HSC numbers contributed to enhanced expansion in bone marrow transplantation assays, but did not affect multilineage repopulation or stress responses. These results affirm that the Scl +19 enhancer plays a key role in the development of hematopoietic stem/progenitor cells, but is not necessary for mature hematopoietic lineages. Moreover, active histone marks across the Scl locus were significantly reduced in Scl(Δ19/Δ19) fetal liver cells without major changes in steady-state messenger RNA levels, suggesting post-transcriptional compensation for loss of a regulatory element, a result that might be widely relevant given the frequent observation of mild phenotypes after deletion of regulatory elements.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Secuencia de Bases / Regulación de la Expresión Génica / Proteínas Proto-Oncogénicas / Elementos de Facilitación Genéticos / Eliminación de Secuencia / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico Límite: Animals Idioma: En Revista: Exp Hematol Año: 2012 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Secuencia de Bases / Regulación de la Expresión Génica / Proteínas Proto-Oncogénicas / Elementos de Facilitación Genéticos / Eliminación de Secuencia / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico Límite: Animals Idioma: En Revista: Exp Hematol Año: 2012 Tipo del documento: Article Pais de publicación: Países Bajos