| Autor: |
Capron, Claude, Lécluse, Yann, Kaushik, Anna Lila, Foudi, Adlen, Lacout, Catherine, Sekkai, Dalila, Godin, Isabelle, Albagli, Olivier, Poullion, Isabelle, Svinartchouk, Fedor, Schanze, Elisabeth, Vainchenker, William, Sablitzky, Fred, Bennaceur-Griscelli, Annelise, Duménil, Dominique |
| Zdroj: |
Blood; June 2006, Vol. 107 Issue: 12 p4678-4686, 9p |
| Abstrakt: |
Hematopoietic stem cells (HSCs) arise, self-renew, or give rise to all hematopoietic lineages through the effects of transcription factors activated by signaling cascades. Lyl-1encodes a transcription factor containing a basic helix-hoop-helix (bHLH) motif closely related to scl/tal,which controls numerous decisions in embryonic and adult hematopoiesis. We report here that Lyl-1null mice are viable and display normal blood cell counts, except for a reduced number of B cells resulting from a partial block after the pro-B stage. Nevertheless, the deletion of Lyl-1results in a diminution in the frequency of immature progenitors (Lin–, CD34–, sca-1+, c-kit+[LSK], and LSK-side population [LSK-SP]) and in S12colony-forming unit (CFU-S12) and long-term culture-initiating cell (LTC-IC) content in embryonic day 14 fetal liver (E14 FL) and adult bone marrow (BM). More important, Lyl-1–/–E14 FL cells and BM are severely impaired in their competitive reconstituting abilities, especially with respect to B and T lineage reconstitution. Thus, ablation of Lyl-1quantitatively and functionally affects HSCs, a cell population that transcribes Lyl-1more actively than their differentiated progenies. Our results demonstrate for the first time that Lyl-1functions are important for HSC properties and B-cell differentiation and that they are largely distinct from sclfunctions. |
| Databáze: |
Supplemental Index |
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