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Direct Induction of Hemogenic Endothelium and Blood by Overexpression of Transcription Factors in Human Pluripotent Stem Cells
Published on: December 3, 2015
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Growth hormone directly stimulates GATA2 expression
Mana Mitsutani1, Midori Matsushita1, Mei Yokoyama1
1Medicine & Clinical Science, Faculty of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Hyogo 663-8179, Japan.
Summary
Growth hormone (GH) directly stimulates GATA2 expression through the GHR/JAK/STAT pathway. This finding clarifies the upstream regulation of GATA2, crucial for pituitary and hematopoietic development.
Area of Science:
- Endocrinology
- Molecular Biology
- Developmental Biology
Background:
- GATA2 is a critical transcription factor for thyrotroph and gonadotroph differentiation in the pituitary and for hematopoietic development.
- Upstream regulators of the GATA2 signaling pathway are not well-understood.
- Growth hormone (GH) is investigated as a potential upstream ligand for GATA2.
Purpose of the Study:
- To investigate the role of GH in regulating GATA2 expression.
- To elucidate the signaling pathway mediating GH-induced GATA2 expression.
- To identify the direct interaction between GH and GATA2.
Main Methods:
- Utilized murine TtT/GF thyrotrophic pituitary tumor cells.
- Employed reporter assays, real-time quantitative PCR, and western blotting to assess GH-induced GATA2 expression.
- Analyzed the impact on the Growth Hormone Receptor (GHR)/Janus Kinase (JAK)/Signal Transducer and Activator of Transcription 5 (STAT5) pathway.
Main Results:
- GH stimulation led to a dose-dependent increase in GATA2 expression.
- Activated STAT5B correlated with increased GATA2 expression, which was inhibited by a STAT5-specific inhibitor.
- Identified functional STAT5B binding sites within the GATA2 promoter region (-359 bp).
Conclusions:
- GH directly stimulates GATA2 expression via the GHR/JAK/STAT pathway.
- This mechanism highlights GH's role in developmental processes regulated by GATA2.
- Provides a molecular basis for GH's influence on pituitary and hematopoietic development.
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