PUBLICATION
Activating transcription factor 3 coordinates differentiation of cardiac and hematopoietic progenitors by regulating glucose metabolism
- Authors
- Yin, H.M., Yan, L.F., Liu, Q., Peng, Z., Zhang, C.Y., Xia, Y., Su, D., Gu, A.H., Zhou, Y.
- ID
- ZDB-PUB-200606-7
- Date
- 2020
- Source
- Science advances 6: eaay9466 (Journal)
- Registered Authors
- Zhou, Yong
- Keywords
- none
- MeSH Terms
-
- Activating Transcription Factor 3*/genetics
- Activating Transcription Factor 3*/metabolism
- Animals
- Cell Differentiation/genetics
- Cyclic AMP Response Element-Binding Protein
- Glucose
- Heart
- Zebrafish*/metabolism
- PubMed
- 32494702 Full text @ Sci Adv
Citation
Yin, H.M., Yan, L.F., Liu, Q., Peng, Z., Zhang, C.Y., Xia, Y., Su, D., Gu, A.H., Zhou, Y. (2020) Activating transcription factor 3 coordinates differentiation of cardiac and hematopoietic progenitors by regulating glucose metabolism. Science advances. 6:eaay9466.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping