| First Author | Spensberger D | Year | 2012 |
| Journal | Exp Hematol | Volume | 40 |
| Issue | 7 | Pages | 588-598.e1 |
| PubMed ID | 22401818 | Mgi Jnum | J:203178 |
| Mgi Id | MGI:5525069 | Doi | 10.1016/j.exphem.2012.02.006 |
| Citation | Spensberger D, et al. (2012) Deletion of the Scl +19 enhancer increases the blood stem cell compartment without affecting the formation of mature blood lineages. Exp Hematol 40(7):588-598.e1 |
| abstractText | 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(Delta19/Delta19)) 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(Delta19/Delta19) 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(Delta19/Delta19) 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. |
