PMID- 27259979
OWN - NLM
STAT- MEDLINE
DCOM- 20170803
LR  - 20220331
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 128
IP  - 4
DP  - 2016 Jul 28
TI  - GATA2 regulates dendritic cell differentiation.
PG  - 508-18
LID - 10.1182/blood-2016-02-698118 [doi]
AB  - Dendritic cells (DCs) are critical immune response regulators; however, the 
      mechanism of DC differentiation is not fully understood. Heterozygous germ line 
      GATA2 mutations induce GATA2-deficiency syndrome, characterized by monocytopenia, 
      a predisposition to myelodysplasia/acute myeloid leukemia, and a profoundly 
      reduced DC population, which is associated with increased susceptibility to viral 
      infections, impaired phagocytosis, and decreased cytokine production. To define 
      the role of GATA2 in DC differentiation and function, we studied Gata2 
      conditional knockout and haploinsufficient mice. Gata2 conditional deficiency 
      significantly reduced the DC count, whereas Gata2 haploinsufficiency did not 
      affect this population. GATA2 was required for the in vitro generation of DCs 
      from Lin(-)Sca-1(+)Kit(+) cells, common myeloid-restricted progenitors, and 
      common dendritic cell precursors, but not common lymphoid-restricted progenitors 
      or granulocyte-macrophage progenitors, suggesting that GATA2 functions in the 
      myeloid pathway of DC differentiation. Moreover, expression profiling 
      demonstrated reduced expression of myeloid-related genes, including mafb, and 
      increased expression of T-lymphocyte-related genes, including Gata3 and Tcf7, in 
      Gata2-deficient DC progenitors. In addition, GATA2 was found to bind an enhancer 
      element 190-kb downstream region of Gata3, and a reporter assay exhibited 
      significantly reduced luciferase activity after adding this enhancer region to 
      the Gata3 promoter, which was recovered by GATA sequence deletion within Gata3 
      +190. These results suggest that GATA2 plays an important role in cell-fate 
      specification toward the myeloid vs T-lymphocyte lineage by regulating 
      lineage-specific transcription factors in DC progenitors, thereby contributing to 
      DC differentiation.
CI  - (c) 2016 by The American Society of Hematology.
FAU - Onodera, Koichi
AU  - Onodera K
AD  - Department of Hematology and Rheumatology.
FAU - Fujiwara, Tohru
AU  - Fujiwara T
AD  - Department of Hematology and Rheumatology, Molecular Hematology/Oncology, and.
FAU - Onishi, Yasushi
AU  - Onishi Y
AD  - Department of Hematology and Rheumatology.
FAU - Itoh-Nakadai, Ari
AU  - Itoh-Nakadai A
AD  - Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan;
FAU - Okitsu, Yoko
AU  - Okitsu Y
AD  - Department of Hematology and Rheumatology.
FAU - Fukuhara, Noriko
AU  - Fukuhara N
AD  - Department of Hematology and Rheumatology.
FAU - Ishizawa, Kenichi
AU  - Ishizawa K
AD  - Department of Hematology and Rheumatology, Department of Hematology and Cell 
      Therapy, Yamagata University Faculty of Medicine, Yamagata, Japan; and.
FAU - Shimizu, Ritsuko
AU  - Shimizu R
AD  - Molecular Hematology and.
FAU - Yamamoto, Masayuki
AU  - Yamamoto M
AD  - Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, 
      Japan.
FAU - Harigae, Hideo
AU  - Harigae H
AD  - Department of Hematology and Rheumatology, Molecular Hematology/Oncology, and.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160603
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (GATA2 Transcription Factor)
RN  - 0 (GATA3 Transcription Factor)
RN  - 0 (Gata2 protein, mouse)
RN  - 0 (Gata3 protein, mouse)
RN  - 0 (Hepatocyte Nuclear Factor 1-alpha)
RN  - 0 (Hnf1a protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/genetics/*immunology
MH  - Dendritic Cells/cytology/*immunology
MH  - GATA2 Transcription Factor/genetics/*immunology
MH  - GATA3 Transcription Factor/genetics/immunology
MH  - Hepatocyte Nuclear Factor 1-alpha/genetics/immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Myeloid Cells/cytology/immunology
MH  - T-Lymphocytes/cytology/immunology
PMC - PMC5026465
EDAT- 2016/06/05 06:00
MHDA- 2017/08/05 06:00
PMCR- 2016/07/28
CRDT- 2016/06/05 06:00
PHST- 2016/02/04 00:00 [received]
PHST- 2016/05/18 00:00 [accepted]
PHST- 2016/06/05 06:00 [entrez]
PHST- 2016/06/05 06:00 [pubmed]
PHST- 2017/08/05 06:00 [medline]
PHST- 2016/07/28 00:00 [pmc-release]
AID - S0006-4971(20)34305-6 [pii]
AID - 2016/698118 [pii]
AID - 10.1182/blood-2016-02-698118 [doi]
PST - ppublish
SO  - Blood. 2016 Jul 28;128(4):508-18. doi: 10.1182/blood-2016-02-698118. Epub 2016 
      Jun 3.