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.
Maeda
Takahiro
T
Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Merghoub
Taha
T
Hobbs
Robin M
RM
Dong
Lin
L
Maeda
Manami
M
Zakrzewski
Johannes
J
van den Brink
Marcel R M
MR
Zelent
Arthur
A
Shigematsu
Hirokazu
H
Akashi
Koichi
K
Teruya-Feldstein
Julie
J
Cattoretti
Giorgio
G
Pandolfi
Pier Paolo
PP
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D017353:Gene Deletion; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D011519:Proto-Oncogenes; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
D004268:DNA-Binding Proteins; D051880:Receptors, Notch; D014157:Transcription Factors; C117093:Zbtb7a protein, mouse