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Cited by 262Mast cells and histamineHematopoietic Stem Cell TransplantationGenomics and Chromatin Dynamics

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Cooperative and Antagonistic Interplay between PU.1 and GATA-2 in the Specification of Myeloid Cell Fates

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Walsh, Jonathan C., DeKoter, Rodney P., Lee, Hyun-Jun, Smith, Erica D., Lancki, David W., Gurish, Michael F., Friend, Daniel S., Stevens, Richard L., Anastasi, John, Singh, Harinder·2002·Immunity
DOI 10.1016/s1074-7613(02)00452-1
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Abstract

PU.1 and GATA transcription factors appear to antagonize each other's function in the development of distinct lineages of the hematopoietic system. In contrast, we demonstrate that PU.1, like GATA-2, is essential for the generation of mast cells. PU.1-/- hematopoietic progenitors can be propagated in IL-3 and differentiate into mast cells or macrophages upon restoration of PU.1 activity. Using these progenitors and a conditionally activatable PU.1 protein, we show that PU.1 can negatively regulate expression of the GATA-2 gene. In the absence of GATA-2, PU.1 promotes macrophage but not mast cell differentiation. Reexpression of GATA-2 in such progenitors enables the generation of mast cells. We propose a developmental model in which cooperative function or antagonistic crossregulation by PU.1 of GATA-2 promotes distinct myeloid cell fates.

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Research works printed but not linked: 26

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Metadata

Authors
Walsh, J. C., DeKoter, R. P., Lee, H.-J., Smith, E. D., Lancki, D. W., Gurish, M. F., Friend, D. S., Stevens, R. L., Anastasi, J., & Singh, H.
Affiliations
  • University of Chicago (US)
  • Howard Hughes Medical Institute (US)
  • Brigham and Women's Hospital (US)
Corresponding author
Singh, Harinder
ORCID
Venue
Immunity
Publisher
Elsevier BV
Published
2002-11
Volume
17
Issue
5
Pages
665-676
ISSN
1074-7613 (ISSN-L)
DOI
10.1016/s1074-7613(02)00452-1
OpenAlex
W2145064410
Cited by
262
References
0
Citations by year
2026: 4 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 3 · 2021: 10 · 2020: 7 · 2019: 7 · 2018: 7 · 2017: 8 · 2016: 11 · 2015: 16 · 2014: 18 · 2013: 8 · 2012: 11
FWCI
4.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (HL07237, HL-36110, P01HL036110)
  • National Institute of General Medical Sciences (GM07151, T32GM007151)
  • National Institute of Allergy and Infectious Diseases (AI-23483, AI31599, R01AI023483)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
PU.1, GATA2, mast cell differentiation, macrophage differentiation, hematopoietic progenitor cells, transcription factors
MeSH terms
Proto-Oncogene Protein Spi-1, Animals, DNA-Binding Proteins, Macrophages, Mast Cells, Proto-Oncogene Proteins, Transcription Factors, Trans-Activators, Zinc Fingers, Gene Expression Regulation, Developmental, Cell Lineage, Myelopoiesis, GATA2 Transcription Factor, Mice

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