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PMID: 15867096 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

PU.1 regulates the commitment of adult hematopoietic progenitors and restricts granulopoiesis.

The Journal of experimental medicine ·Vol. 201 ·No. 9 ·2005-05-02 ·Pages 1487-502

Dakic A, Metcalf D, Di Rago L, Mifsud S, Wu L, Nutt SL

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.

MeSH Terms
Animals Antibodies, Monoclonal Blood Cell Count Blotting, Western Cell Differentiation/physiology Cells, Cultured Colony-Forming Units Assay DNA Primers Flow Cytometry Genetic Vectors Genotype Granulocytes/metabolism,physiology Green Fluorescent Proteins Hematopoietic Stem Cells/metabolism,physiology Mice Mice, Inbred C57BL Mice, Transgenic Myeloid Cells/metabolism,physiology Proto-Oncogene Proteins/metabolism Reverse Transcriptase Polymerase Chain Reaction Trans-Activators/metabolism
Chemicals
Antibodies, Monoclonal DNA Primers Proto-Oncogene Proteins Trans-Activators proto-oncogene protein Spi-1 Green Fluorescent Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Dakic Aleksandar
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Metcalf Donald
Di Rago Ladina
Mifsud Sandra
Wu Li
Nutt Stephen L
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20050075
Published
2005-05-02
Pages
1487-502
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2213186
Subset
IM
Grants
NCI NIH HHS · R01 CA022556 · United States
NCI NIH HHS · R37 CA022556 · United States
NCI NIH HHS · CA22556 · United States
External Links
PubMed source DOI: 10.1084/jem.20050075 PMC Full Text View journal details
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