PUBLICATION
Copper overload impairs hematopoietic stem and progenitor cell proliferation via prompting HSF1/SP1 aggregation and the subsequently downregulating FOXM1-Cytoskeleton axis
- Authors
- Li, L., Tai, Z., Liu, W., Luo, Y., Wu, Y., Lin, S., Liu, M., Gao, B., Liu, J.X.
- ID
- ZDB-PUB-230404-51
- Date
- 2023
- Source
- iScience 26: 106406106406 (Journal)
- Registered Authors
- Liu, Jing-xia, Liu, Mugen, Wu, You
- Keywords
- Cell biology, Molecular biology, Stem cells research
- MeSH Terms
- none
- PubMed
- 37009226 Full text @ iScience
Citation
Li, L., Tai, Z., Liu, W., Luo, Y., Wu, Y., Lin, S., Liu, M., Gao, B., Liu, J.X. (2023) Copper overload impairs hematopoietic stem and progenitor cell proliferation via prompting HSF1/SP1 aggregation and the subsequently downregulating FOXM1-Cytoskeleton axis. iScience. 26:106406106406.
Abstract
Unbalanced Cu homeostasis has been suggested to be associated with hematopoietic disease, but the roles of Cu overload in the hematopoietic system and the potential mechanisms are obscure. Here, we report a novel association and the novel potential pathways for Cu overload to induce proliferation defects in zebrafish embryonic hematopoietic stem and progenitor cells (HSPCs) via down-regulating expression of foxm1-cytoskeleton axis, which is conserved from fish to mammals. Mechanistically, we show the direct binding of Cu to transcriptional factors HSF1 and SP1 and that Cu overload induces the cytoplasmic aggregation of proteins HSF1 and SP1. These result in the reduced transcriptional activities of HSF1 and SP1 on their downstream FOXM1 as well as the FOXM1 transcriptional activities on cytoskeletons in HSPCs, which leads to ultimately cell proliferation impairment. These findings unveil the novel linkage of Cu overload with specific signaling transduction as well as the subsequent HSPC proliferation defects.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping