GATA2 is critical for the maintenance of cellular identity in differentiated mast cells derived from mouse bone marrow

Ohmori, S; Moriguchi, Takashi; Noguchi, Yuki; Ikeda, Muneharu; Kobayashi, K.; Tomaru, Nazuki; Ishijima, Yasushi; Onodera, Osamu; Yamamoto, Masayuki; Ohneda, Kinuko

doi:10.1182/blood-2014-11-612465

Cited by 44 publications

(57 citation statements)

References 42 publications

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“…On the other hand, genes that are upregulated upon Nanog induction are highly enriched in the mast cell program (Fig EV3A and B; Dataset EV1). This is accompanied by an upregulation of Gata2 (Salmon et al, 2007), a critical specifier of mast cells (Ohmori et al, 2015), that we also see increased upon Nanog expression in MEPs (Fig EV3B; Dataset EV1). This is accompanied by an upregulation of Gata2 (Salmon et al, 2007), a critical specifier of mast cells (Ohmori et al, 2015), that we also see increased upon Nanog expression in MEPs (Fig EV3B; Dataset EV1).…”

Section: Esc-derived Embryoid Bodiessupporting

confidence: 52%

The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1

et al. 2019

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Progenitors of the first hematopoietic cells in the mouse arise in the early embryo from Brachyury‐positive multipotent cells in the posterior‐proximal region of the epiblast, but the mechanisms that specify primitive blood cells are still largely unknown. Pluripotency factors maintain uncommitted cells of the blastocyst and embryonic stem cells in the pluripotent state. However, little is known about the role played by these factors during later development, despite being expressed in the postimplantation epiblast. Using a dual transgene system for controlled expression at postimplantation stages, we found that Nanog blocks primitive hematopoiesis in the gastrulating embryo, resulting in a loss of red blood cells and downregulation of erythropoietic genes. Accordingly, Nanog‐deficient embryonic stem cells are prone to erythropoietic differentiation. Moreover, Nanog expression in adults prevents the maturation of erythroid cells. By analysis of previous data for NANOG binding during stem cell differentiation and CRISPR/Cas9 genome editing, we found that Tal1 is a direct NANOG target. Our results show that Nanog regulates primitive hematopoiesis by directly repressing critical erythroid lineage specifiers.

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Section: Esc-derived Embryoid Bodiessupporting

confidence: 52%

The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1

et al. 2019

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“…The hub genes in the magenta module were KIT (CD117; stem cell growth factor receptor) and KITLG which are indispensable for the growth, differentiation, survival, and homing of mast cells. 36,37 The hub gene CD44, an adhesion molecule, has been associated with asthma and plays a key role in mediating the adhesion of mast cells to bronchial smooth muscle. [33][34][35] GATA2, a zinc finger transcription factor of the GATA family, is critical in driving the differentiation of prebasophil and mast cell progenitors into basophils and mast cells, respectively, and also plays a role in the maintenance of basophil and mast cell repertoires.…”

Section: Modulementioning

confidence: 99%

Identification of surrogate prognostic biomarkers for allergic asthma in nasal epithelial brushing samples by WGCNA

Liu

Fang

et al. 2018

J of Cellular Biochemistry

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Background Allergic asthma is a lower respiratory tract disease of Th2 inflammation with multiple molecular mechanisms. The upper and lower airways can be unified by the concept of a united airway and, as such, gene expression studies of upper epithelial cells may provide effective surrogate biomarkers for the prognostic study of allergic asthma. Objective To identify surrogate biomarkers in upper airway epithelial cells for the prognostic study of allergic asthma. Methods Nasal epithelial cell gene expression in 40 asthmatic and 17 healthy control subjects were analyzed by weighted gene coexpression network analysis (WGCNA) to identify gene network modules and profiles in allergic asthma. Functional enrichment analysis was performed on the coexpression genes in certain highlighted modules. Results A total of 13 coexpression modules were constructed by WGCNA from 2804 genes in nasal epithelial brushing samples of the 40 asthmatic and 17 healthy subjects. The number of genes in these modules ranged from 1086 (Turquoise module) to 45 (Salmon). Eight coexpression modules were found to be significantly correlated (P < 0.05) with two clinic traits, namely disease status, and severity. Four modules were positively correlated ( P < 0.05) with the traits and these, therefore, contained genes that are mostly overexpressed in asthma. Contrastingly, the four other modules were found to be negatively correlated with the clinic traits. Functional enrichment analysis of the positively correlated modules showed that one (Magenta) was mainly enriched in mast cell activation and degranulation; another (Pink) was largely involved in immune cell response; the third (Yellow) was predominantly enriched in transmembrane signal pathways; and the last (Blue) was mainly enriched in substructure components of the cells. The hub genes in the modules were KIT, KITLG, GATA2, CD44, PTPRC, and CFTR, and these were confirmed as having significantly higher expression in the nasal epithelial cells. Combining the six hub genes enabled a relatively high capacity for discrimination between asthmatics and healthy subjects with an area under the receiver operating characteristic (ROC) curve of 0.924. Conclusions Our findings provide a framework of coexpression gene modules from nasal epithelial brushing samples that could be used for the prognostic study of allergic asthma.

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“…2). For the maintenance phase, STAT5, GATA2, and C/EBPα have also been demonstrated to play a critical role in basophil maintenance [72,45], while STAT5, GATA2 and MITF have also been demonstrated to play a crucial role in mast cell maintenance [72,45,73] (Fig. 2).…”

Section: C/ebpα Is the Critical Basophil Transcription Factor For Spementioning

confidence: 99%

Transcriptional regulation of mast cell and basophil lineage commitment

Huang

Liu

2016

Semin Immunopathol

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Basophils and mast cells have long been known to play critical roles in allergic disease and in immunity against parasitic infection. Accumulated evidence supports that basophils and mast cells also have important roles in immune regulations, host defense against bacteria and viruses, and autoimmune diseases. However, origin and molecular regulation of basophil and mast cell differentiation remain incompletely understood. In this review, we focus on recent advances in the understanding of origin and molecular regulation of mouse and human basophil and mast cell development. A more complete understanding of how basophils and mast cells develop at the molecular level will lead to development of interventions that are more effective in achieving long-term success.

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GATA2 is critical for the maintenance of cellular identity in differentiated mast cells derived from mouse bone marrow

Abstract: Key Points Mouse BM-derived mast cells can dedifferentiate into immature myeloid-like cells after the deletion of the GATA2 DNA binding domain. Increased expression of C/EBPα is critical for the dedifferentiation of GATA2-deficient mast cells.

Cited by 44 publications

References 42 publications

The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1

The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1

Identification of surrogate prognostic biomarkers for allergic asthma in nasal epithelial brushing samples by WGCNA

Transcriptional regulation of mast cell and basophil lineage commitment

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