Stem cell fate specification: role of master regulatory switch transcription factor PU.1 in differential hematopoiesis.
PU.1 is a versatile hematopoietic cell-specific ETS-family transcriptional regulator required for the development of both the inborn and the adaptive immunity, owing to its potential ability to regulate the expression of multiple genes specific for different lineages during normal hematopoiesis. It functions in a cell-autonomous manner to control the proliferation and differentiation, predominantly of lymphomyeloid progenitors, by binding to the promoters of many myeloid genes including the macrophage colony-stimulating factor (M-CSF) receptor, granulocyte-macrophage (GM)-CSF receptor alpha, and CD11b. In B cells, it regulates the immunoglobulin lambda 2-4 and kappa 3' enhancers, and J chain promoters. Besides lineage development, PU.1 also directs homing and long-term engraftment of hematopoietic progenitors to the bone marrow. PU.1 gene disruption causes a cell-intrinsic defect in hematopoietic progenitor cells, recognized by an aberrant myeloid and B lymphoid development. It also immortalizes erythroblasts when overexpressed in many cell lines. Although a number of reviews have been published on its functional significance, in the following review we attempted to consolidate information about the differential participation and role of transcription factor PU.1 at various stages of hematopoietic development beginning from stem cell proliferation, lineage commitment and terminal differentiation into distinct blood cell types, and leukemogenesis.
Gangenahalli
Gurudutta U
GU
Stem Cell Gene Therapy Research Group, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Delhi-110054, India. gugdutta@hotmail.com
Gupta
Pallavi
P
Saluja
Daman
D
Verma
Yogesh K
YK
Kishore
Vimal
V
Chandra
Ramesh
R
Sharma
R K
RK
Ravindranath
T
T
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D039481:CD11b Antigen / Q000096:biosynthesis; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D019070:Cell Lineage; D049109:Cell Proliferation; D004742:Enhancer Elements, Genetic; D004912:Erythrocytes / Q000166:cytology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D000099232:Proto-Oncogene Protein Spi-1
D039481:CD11b Antigen; D007146:Immunoglobulin lambda-Chains; D011518:Proto-Oncogene Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1