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PMID:16514064

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Citation

Capron, C, Lécluse, Y, Kaushik, AL, Foudi, A, Lacout, C, Sekkai, D, Godin, I, Albagli, O, Poullion, I, Svinartchouk, F, Schanze, E, Vainchenker, W, Sablitzky, F, Bennaceur-Griscelli, A and Duménil, D (2006) The SCL relative LYL-1 is required for fetal and adult hematopoietic stem cell function and B-cell differentiation. Blood 107:4678-86

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.

Links

PubMed Online version:10.1182/blood-2005-08-3145

Keywords

Animals; B-Lymphocytes/cytology; B-Lymphocytes/physiology; Basic Helix-Loop-Helix Transcription Factors/deficiency; Basic Helix-Loop-Helix Transcription Factors/metabolism; Cell Differentiation/physiology; Cell Lineage/physiology; Embryonic Development/physiology; Gene Deletion; Gene Expression Regulation, Developmental/physiology; Hematopoiesis/physiology; Hematopoietic Stem Cells/cytology; Hematopoietic Stem Cells/physiology; Mice; Neoplasm Proteins/deficiency; Neoplasm Proteins/metabolism; Proto-Oncogene Proteins/metabolism; T-Lymphocytes/cytology; T-Lymphocytes/physiology; Transcription, Genetic/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:LYL1

involved_in

GO:0030183: B cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:LYL1

involved_in

GO:0060216: definitive hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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