PU.1 regulates the commitment of adult hematopoietic progenitors and restricts granulopoiesis
Details
Publication Year 2005-05-02, Volume 201, Issue #9, Page 1487-1502
Journal Title
JOURNAL OF EXPERIMENTAL MEDICINE
Publication Type
Journal Article
Abstract
Although the transcription factor PU.1 is essential for fetal lymphomyelopoiesis, we unexpectedly found that elimination of the gene in adult mice allowed disturbed hematopoiesis, dominated by granulocyte production. Impaired production of lymphocytes was evident in PU.1-deficient bone marrow (BM), but myelocytes and clonogenic granulocytic progenitors that are responsive to granulocyte colony-stimulating factor or interleukin-3 increased dramatically. No identifiable common lymphoid or myeloid progenitor populations were discernable by flow cytometry; however, clonogenic assays suggested an overall increased frequency of blast colony-forming cells and BM chimeras revealed existence of long-term self-renewing PU.1-deficient cells that required PU.1 for lymphoid, but not granulocyte, generation. PU.1 deletion in granulocyte-macrophage progenitors, but not in common myeloid progenitors, resulted in excess granulocyte production; this suggested specific roles of PU.1 at different stages of myeloid development. These findings emphasize the distinct nature of adult hematopoiesis and reveal that PU.1 regulates the specification of the multipotent lymphoid and myeloid compartments and restrains, rather than promotes, granulopoiesis.
Publisher
ROCKEFELLER UNIV PRESS
Keywords
TRANSCRIPTION FACTOR PU.1; COLONY-STIMULATING FACTOR; COMMON LYMPHOID PROGENITORS; B-CELL DEVELOPMENT; FETAL LIVER; STEM-CELLS; MYELOID PROGENITORS; NEGATIVE REGULATOR; SELF-RENEWAL; BONE-MARROW
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2005-05-02 12:00:00
Last Modified: 0001-01-01 12:00:00
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