PUBLICATION
The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis
- Authors
- He, X., Ge, C., Xia, J., Xia, Z., Zhao, L., Huang, S., Wang, R., Pan, J., Cheng, T., Xu, P.F., Wang, F., Min, J.
- ID
- ZDB-PUB-230418-57
- Date
- 2023
- Source
- Advanced science (Weinheim, Baden-Wurttemberg, Germany) 10(17): e2205345 (Journal)
- Registered Authors
- Wang, Fudi, Xia, Zhidan
- Keywords
- HSPCs, SLC39A10, ZIP10, anemia, hematopoiesis, hematopoietic stem cells, zinc homeostasis
- MeSH Terms
-
- Animals
- Hematopoiesis*
- Mice
- Zebrafish*/metabolism
- Zinc/metabolism
- Iron
- PubMed
- 37068188 Full text @ Adv Sci (Weinh)
Citation
He, X., Ge, C., Xia, J., Xia, Z., Zhao, L., Huang, S., Wang, R., Pan, J., Cheng, T., Xu, P.F., Wang, F., Min, J. (2023) The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis. Advanced science (Weinheim, Baden-Wurttemberg, Germany). 10(17):e2205345.
Abstract
The role of zinc in hematopoiesis is currently unclear. Here, SLC39A10 (ZIP10) is identified as a key zinc transporter in hematopoiesis. The results show that in zebrafish, Slc39a10 is a key regulator of the response to zinc deficiency. Surprisingly, both slc39a10 mutant zebrafish and hematopoietic Slc39a10-deficient mice develop a more severe form of impaired hematopoiesis than animals lacking transferrin receptor 1, a well-characterized iron gatekeeper, indicating that zinc plays a larger role than iron in hematopoiesis, at least in early hematopoietic stem cells (HSCs). Furthermore, it is shown that loss of Slc39a10 causes zinc deficiency in fetal HSCs, which in turn leads to DNA damage, apoptosis, and G1 cell cycle arrest. Notably, zinc supplementation largely restores colony formation in HSCs derived from hematopoietic Slc39a10-deficient mice. In addition, inhibiting necroptosis partially restores hematopoiesis in mouse HSCs, providing mechanistic insights into the requirement for zinc in mediating hematopoiesis. Together, these findings indicate that SLC39A10 safeguards hematopoiesis by protecting against zinc deficiency-induced necroptosis, thus providing compelling evidence that SLC39A10 and zinc homeostasis promote the development of fetal HSCs. Moreover, these results suggest that SLC39A10 may serve as a novel therapeutic target for treating anemia and zinc deficiency-related disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping