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Regulation of B versus T lymphoid lineage fate decision by the proto-oncogene LRF.

Hematopoietic stem cells in the bone marrow give rise to lymphoid progenitors, which subsequently differentiate into B and T lymphocytes. Here we show that the proto-oncogene LRF plays an essential role in the B versus T lymphoid cell-fate decision. We demonstrate that LRF is key for instructing early lymphoid progenitors in mice to develop into B lineage cells by repressing T cell-instructive signals produced by the cell-fate signal protein, Notch. We propose a new model for lymphoid lineage commitment, in which LRF acts as a master regulator of the cell's determination of B versus T lineage.

Pubmed ID: 17495164

Authors

  • Maeda T
  • Merghoub T
  • Hobbs RM
  • Dong L
  • Maeda M
  • Zakrzewski J
  • van den Brink MR
  • Zelent A
  • Shigematsu H
  • Akashi K
  • Teruya-Feldstein J
  • Cattoretti G
  • Pandolfi PP

Journal

Science (New York, N.Y.)

Publication Data

May 11, 2007

Associated Grants

  • Agency: NCI NIH HHS, Id: CA-102142
  • Agency: NCI NIH HHS, Id: R01 CA102142
  • Agency: NCI NIH HHS, Id: R01 CA102142-06A1

Mesh Terms

  • Animals
  • B-Lymphocytes
  • Bone Marrow Cells
  • Cell Lineage
  • Cells, Cultured
  • DNA-Binding Proteins
  • Gene Deletion
  • Hematopoietic Stem Cells
  • Lymphopoiesis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Proto-Oncogenes
  • Receptors, Notch
  • Signal Transduction
  • T-Lymphocytes
  • Thymus Gland
  • Transcription Factors