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The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis

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...

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Autores principales: He, Xuyan, Ge, Chaodong, Xia, Jun, Xia, Zhidan, Zhao, Lu, Huang, Sicong, Wang, Rong, Pan, Jianwei, Cheng, Tao, Xu, Peng‐Fei, Wang, Fudi, Min, Junxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10265086/
https://www.ncbi.nlm.nih.gov/pubmed/37068188
http://dx.doi.org/10.1002/advs.202205345
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author He, Xuyan
Ge, Chaodong
Xia, Jun
Xia, Zhidan
Zhao, Lu
Huang, Sicong
Wang, Rong
Pan, Jianwei
Cheng, Tao
Xu, Peng‐Fei
Wang, Fudi
Min, Junxia
author_facet He, Xuyan
Ge, Chaodong
Xia, Jun
Xia, Zhidan
Zhao, Lu
Huang, Sicong
Wang, Rong
Pan, Jianwei
Cheng, Tao
Xu, Peng‐Fei
Wang, Fudi
Min, Junxia
author_sort He, Xuyan
collection PubMed
description 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 G(1) 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.
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spelling pubmed-102650862023-06-15 The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis He, Xuyan Ge, Chaodong Xia, Jun Xia, Zhidan Zhao, Lu Huang, Sicong Wang, Rong Pan, Jianwei Cheng, Tao Xu, Peng‐Fei Wang, Fudi Min, Junxia Adv Sci (Weinh) Research Articles 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 G(1) 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. John Wiley and Sons Inc. 2023-04-17 /pmc/articles/PMC10265086/ /pubmed/37068188 http://dx.doi.org/10.1002/advs.202205345 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
He, Xuyan
Ge, Chaodong
Xia, Jun
Xia, Zhidan
Zhao, Lu
Huang, Sicong
Wang, Rong
Pan, Jianwei
Cheng, Tao
Xu, Peng‐Fei
Wang, Fudi
Min, Junxia
The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis
title The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis
title_full The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis
title_fullStr The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis
title_full_unstemmed The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis
title_short The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis
title_sort zinc transporter slc39a10 plays an essential role in embryonic hematopoiesis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10265086/
https://www.ncbi.nlm.nih.gov/pubmed/37068188
http://dx.doi.org/10.1002/advs.202205345
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