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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4678-4686.
Prepublished online as a Blood First Edition Paper on March 2, 2006; DOI 10.1182/blood-2005-08-3145.
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Submitted August 4, 2005
Accepted January 26, 2006
The SCL relative LYL-1 is required for fetal and adult hematopoietic stem cell functions and B cell differentiation
Claude Capron, Yann Lecluse, Anna L Kaushik, Adlen Foudi, Catherine Lacout, Dalila Sekkai, Isabelle Godin, Olivier Albagli, Isabelle Poullion, Fedor Svinartchouk, Elisabeth Schanze, William Vainchenker*, Fred Sablitzky, Annelise Bennaceur-Griscelli, and Dominique Dumenil
INSERM U362, Institut Gustave Roussy, Villejuif, France; Laboratoire d'Hematologie et d'Immunologie, Faculte de Medecine Versailles, Garches, France
IFR 54, Institut Gustave Roussy, Villejuif, France
INSERM U362, Institut Gustave Roussy, Villejuif, France
Genethon, Evry, France
University of Nottingham, School of Biology, Institute of Genetics, Queen's Medical Center, Nottingham, United Kingdom
Departement d'Hematologie, Institut Cochin, Paris, France
* Corresponding author; email: verpre{at}igr.fr.
Hematopoietic stem cells (HSC) arise, self-renew or give rise to all hematopoietic lineages through the effects of transcription factors activated by signaling cascades. Lyl-1 encodes a transcription factor containing a bHLH motif closely related to scl/tal that controls numerous decisions in embryonic and adult hematopoiesis. We report here that lyl-1 null 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, deletion of lyl-1 results in a diminution in the frequency of immature progenitors (Lin-, CD34-, sca-1+, c-kit+ (LSK)and LSK-SP (Side Population)) as well as CFU-S12 and LTC-IC content in embryonic day 14 fetal liver (E14 FL) and adult bone marrow (BM). More importantly, lyl-1-/- E14 FL cells and BM are severely impaired in their competitive reconstituting abilities, especially with respect to B and T lineages reconstitution. Thus, ablation of lyl-1 affects both quantitatively and functionally HSC, a cell population that transcribes lyl-1 more actively than their differentiated progenies. Altogether, our results demonstrate for the first time that lyl-1 functions are important for HSC properties and B differentiation and are largely distinct from scl functions.
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