PUBLICATION
Rnf111 has a pivotal role in regulating development of definitive hematopoietic stem and progenitor cells through the Smad2/3-Gcsfr/NO axis in zebrafish
- Authors
- Liu, X., Sha, J., Wang, L., Wang, Z., Fang, Z., Han, X., Tan, S., Chen, Y., Yuan, H., De The, H., Zhou, J., Zhu, J.
- ID
- ZDB-PUB-241004-14
- Date
- 2024
- Source
- Haematologica : (Journal)
- Registered Authors
- Chen, Yi, Zhu, Jun
- Keywords
- none
- MeSH Terms
-
- Phosphorylation
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Animals
- Hematopoiesis
- Zebrafish*/metabolism
- Signal Transduction*
- Smad2 Protein*/metabolism
- Ubiquitin-Protein Ligases*/genetics
- Ubiquitin-Protein Ligases*/metabolism
- Smad3 Protein*/metabolism
- Hematopoietic Stem Cells*/cytology
- Hematopoietic Stem Cells*/metabolism
- PubMed
- 39363867 Full text @ Haematologica
Citation
Liu, X., Sha, J., Wang, L., Wang, Z., Fang, Z., Han, X., Tan, S., Chen, Y., Yuan, H., De The, H., Zhou, J., Zhu, J. (2024) Rnf111 has a pivotal role in regulating development of definitive hematopoietic stem and progenitor cells through the Smad2/3-Gcsfr/NO axis in zebrafish. Haematologica. :.
Abstract
The ubiquitination or SUMOylation of hematopoietic related factors plays pivotal roles in hematopoiesis. RNF111, known as a ubiquitin ligase (Ubl), is a newly discovered SUMO-targeted ubiquitin ligase (STUbl) involved in multiple signaling pathways mediated by TGF-β family members. However, its role in hematopoiesis remains unclear. Herein, a heritable Rnf111 mutant zebrafish line was generated by CRISPR/Cas9-mediated genome editing. Impaired hematopoietic stem and progenitor cells (HSPC) of definitive hematopoiesis was found in Rnf111 deficient mutants. Ablation of Rnf111 resulted in decreased phosphorylation of Smad2/3 in HSPC. Definitive endoderm 2 inducer (IDE2), which specifically activates TGF-β signaling and downstream Smad2 phosphorylation, can restore the definitive hematopoiesis in Rnf111-deficient embryos. Further molecular mechanism studies revealed that Gcsfr/NO signaling was an important target pathway of Smad2/3 involved in Rnf111-mediated HSPC development. In conclusion, our study demonstrated that Rnf111 contributes to the development of HSPC by maintaining Smad2/3 phosphorylation and the Gcsfr/NO signaling pathway activation. Keywords: Rnf111, Ubiquitin ligase (UbL), HSPC, Smad2/3, Gcsfr/NO.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping