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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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HEMATOPOIESIS

The SCL relative LYL-1 is required for fetal and adult hematopoietic stem cell function and B-cell differentiation

Claude Capron, Yann Lécluse, Anna Lila 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 Duménil

From the Insitut National de la Santé et de la Recherche Médicale (INSERM) U362 and Institut Fédératif de Recherche (IFR) 54, Institut Gustave Roussy, Villejuif; Genethon, Evry; Département d'Hématologie, Institut Cochin, Paris; Laboratoire d'Hématologie et d'Immunologie, Faculté de Médecine Versailles Paris Ouest, Garches, France; and the University of Nottingham, School of Biology, Institute of Genetics, Queen's Medical Center, Nottingham, United Kingdom.

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-1 encodes 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-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, the deletion of Lyl-1 results in a diminution in the frequency of immature progenitors (Lin–, CD34–, sca-1+, c-kit+ [LSK], and LSK-side population [LSK-SP]) and in S12 colony-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-1 quantitatively and functionally affects HSCs, a cell population that transcribes Lyl-1 more actively than their differentiated progenies. Our results demonstrate for the first time that Lyl-1 functions are important for HSC properties and B-cell differentiation and that they are largely distinct from scl functions.


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