title: The SCL relative LYL-1 is required for fetal and adult hematopoietic stem cell function and B-cell differentiation.
abstract: 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 S(12) colony-forming unit (CFU-S(12)) 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicicale (INSERM) U362, Institut Gustave Roussy, 94805 Villejuif, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Capron
authors.forename: Yann
authors.initials: Y
authors.lastname: Lécluse
authors.forename: Anna Lila
authors.initials: AL
authors.lastname: Kaushik
authors.forename: Adlen
authors.initials: A
authors.lastname: Foudi
authors.forename: Catherine
authors.initials: C
authors.lastname: Lacout
authors.forename: Dalila
authors.initials: D
authors.lastname: Sekkai
authors.forename: Isabelle
authors.initials: I
authors.lastname: Godin
authors.forename: Olivier
authors.initials: O
authors.lastname: Albagli
authors.forename: Isabelle
authors.initials: I
authors.lastname: Poullion
authors.forename: Fedor
authors.initials: F
authors.lastname: Svinartchouk
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schanze
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
authors.forename: Fred
authors.initials: F
authors.lastname: Sablitzky
authors.forename: Annelise
authors.initials: A
authors.lastname: Bennaceur-Griscelli
authors.forename: Dominique
authors.initials: D
authors.lastname: Duménil
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009363:Neoplasm Proteins / Q000172:deficiency / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C490130:Lyl1 protein, mouse; C489366:Tal1 protein, mouse