PUBLICATION
ADP receptor P2y12 prevents excessive primitive hematopoiesis in zebrafish by inhibiting Gata1
- Authors
- Li, F.F., Liang, Y.L., Han, X.S., Guan, Y.N., Chen, J., Wu, P., Zhao, X.X., Jing, Q.
- ID
- ZDB-PUB-200620-14
- Date
- 2020
- Source
- Acta Pharmacologica Sinica 42(3): 414-421 (Journal)
- Registered Authors
- Jing, Qing
- Keywords
- Gata1, P2y12, Zebrafish, erythropoiesis, primitive hematopoiesis, purinergic signaling
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Animals, Genetically Modified
- CRISPR-Cas Systems
- Cell Differentiation/physiology
- Embryo, Nonmammalian/physiology
- Endothelium, Vascular/physiology
- Erythrocytes/physiology
- Female
- GATA1 Transcription Factor/antagonists & inhibitors*
- GATA1 Transcription Factor/metabolism
- Gene Expression Regulation, Developmental/physiology
- Gene Knockout Techniques
- Hematopoiesis/genetics
- Hematopoiesis/physiology*
- Male
- Mutation
- Receptors, Purinergic P2Y12/genetics
- Receptors, Purinergic P2Y12/physiology*
- Up-Regulation/physiology
- Zebrafish
- Zebrafish Proteins/antagonists & inhibitors*
- Zebrafish Proteins/metabolism
- PubMed
- 32555443 Full text @ Acta Pharmacol. Sin.
Citation
Li, F.F., Liang, Y.L., Han, X.S., Guan, Y.N., Chen, J., Wu, P., Zhao, X.X., Jing, Q. (2020) ADP receptor P2y12 prevents excessive primitive hematopoiesis in zebrafish by inhibiting Gata1. Acta Pharmacologica Sinica. 42(3):414-421.
Abstract
In the past two decades, purinergic signaling has emerged as a key regulator of hematopoiesis in physiological and pathological conditions. ADP receptor P2y12 is a crucial component of this signaling, but whether it is involved in primitive hematopoiesis remains unknown. To elucidate the function of P2y12 and provide new insights for drug development, we established a zebrafish P2y12 mutant by CRISPR/Cas 9-based genetic modification system, and investigated whether P2y12 acted as an important regulator for primitive hematopoiesis. By using mass spectrometry (MS) combined with RNA sequencing, we showed that absence of P2y12 induced excessive erythropoiesis, evidenced by significantly increased expression of mature erythrocytes marker α-globin (Hbae1 and Hbae3), β-globin (Hbbe1 and Hbbe3). Expression pattern analysis showed that P2y12 was mainly expressed in red blood cells and endothelial cells of early zebrafish embryos. Further studies revealed that primitive erythroid progenitor marker Gata1 was markedly up-regulated. Remarkably, inhibition of Gata1 by injection of Gata1 morpholino could rescue the erythroid abnormality in P2y12 mutants. The present study demonstrates the essential role of purinergic signaling in differentiation of proerythrocytes during primitive hematopoiesis, and provides potential targets for treatment of blood-related disease and drug development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping