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Updated: Dec 19, 2025
Direct Induction of Hemogenic Endothelium and Blood by Overexpression of Transcription Factors in Human Pluripotent Stem Cells
Published on: December 3, 2015
Activating transcription factor 3 coordinates differentiation of cardiac and hematopoietic progenitors by regulating
Hui-Min Yin1, Li-Feng Yan1, Qian Liu2
1CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
Insights
Activating transcription factor 3 (ATF3) is crucial for coordinating cardiac and hematopoietic progenitor development in zebrafish. ATF3 regulates glucose metabolism, preventing differentiation blockade and ensuring proper circulatory system formation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Cardiovascular Research
Background:
- Cardiac and hematopoietic progenitors (CPs and HPs) develop from mesoderm to form the circulatory system.
- Mechanisms coordinating CP and HP differentiation remain largely unknown.
Purpose of the Study:
- Investigate the role of activating transcription factor 3 (ATF3) in coordinating CP and HP development.
- Elucidate the molecular mechanisms underlying ATF3's function in progenitor differentiation.
Main Methods:
- Utilized zebrafish (Danio rerio) as a model organism.
- Generated and analyzed atf3 knockout (atf3-/-) mutants.
- Examined gene expression, cell differentiation, and metabolic pathways.
Main Results:
- atf3 is highly expressed in mesodermal progenitors.
- atf3-/- mutants display atrial dilated cardiomyopathy and myeloid immaturity.
- Loss of atf3 blocks CP and HP differentiation by altering glucose metabolism via cebpγ and slc2a1a.
Conclusions:
- ATF3 is essential for coordinating cardiac and hematopoietic progenitor differentiation.
- ATF3 regulates progenitor development by modulating glucose metabolism and redox state.
- ATF3 provides metabolic adaptability crucial for circulatory system formation.
Abstract:
The cardiac and hematopoietic progenitors (CPs and HPs, respectively) in the mesoderm ultimately form a well-organized circulation system, but mechanisms that reconcile their development remain elusive. We found that activating transcription factor 3 (atf3) was highly expressed in the CPs, HPs, and mesoderm, in zebrafish. The atf3 -/- mutants exhibited atrial dilated cardiomyopathy and a high ratio of immature myeloid cells. These manifestations were primarily caused by the blockade of differentiation of both CPs and HPs within the anterior lateral plate mesoderm. Mechanistically, Atf3 targets cebpγ to repress slc2a1a-mediated glucose utilization. The high rate of glucose metabolism in atf3 -/- mutants inhibited the differentiation of progenitors by changing the redox state. Therefore, atf3 could provide CPs and HPs with metabolic adaptive capacity to changes in glucose levels. Our study provides new insights into the role of atf3 in the coordination of differentiation of CPs and HPs by regulating glucose metabolism.
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