Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Animals
-
B-Lymphocytes / cytology*
-
B-Lymphocytes / physiology
-
Bone Marrow Cells / cytology
-
Cell Lineage
-
Cells, Cultured
-
DNA-Binding Proteins / genetics*
-
DNA-Binding Proteins / physiology
-
Gene Deletion
-
Hematopoietic Stem Cells / cytology*
-
Hematopoietic Stem Cells / physiology
-
Lymphopoiesis*
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Models, Biological
-
Proto-Oncogenes*
-
Receptors, Notch / metabolism*
-
Signal Transduction
-
T-Lymphocytes / cytology*
-
T-Lymphocytes / physiology
-
Thymus Gland / cytology
-
Transcription Factors / genetics*
-
Transcription Factors / physiology
Substances
-
DNA-Binding Proteins
-
Receptors, Notch
-
Transcription Factors
-
Zbtb7a protein, mouse