The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis
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 hemat...
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| Format: | Article |
| Language: | English |
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Wiley
2023-06-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202205345 |
| _version_ | 1827926270152802304 |
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| author | Xuyan He Chaodong Ge Jun Xia Zhidan Xia Lu Zhao Sicong Huang Rong Wang Jianwei Pan Tao Cheng Peng‐Fei Xu Fudi Wang Junxia Min |
| author_facet | Xuyan He Chaodong Ge Jun Xia Zhidan Xia Lu Zhao Sicong Huang Rong Wang Jianwei Pan Tao Cheng Peng‐Fei Xu Fudi Wang Junxia Min |
| author_sort | Xuyan He |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T05:36:44Z |
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| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-13T05:36:44Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-9be81e22e2804831afed8a29041880d82023-06-14T07:18:56ZengWileyAdvanced Science2198-38442023-06-011017n/an/a10.1002/advs.202205345The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic HematopoiesisXuyan He0Chaodong Ge1Jun Xia2Zhidan Xia3Lu Zhao4Sicong Huang5Rong Wang6Jianwei Pan7Tao Cheng8Peng‐Fei Xu9Fudi Wang10Junxia Min11The First Affiliated Hospital The Second Affiliated Hospital Institute of Translational Medicine School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine 310058 Hangzhou ChinaThe First Affiliated Hospital The Second Affiliated Hospital Institute of Translational Medicine School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine 310058 Hangzhou ChinaState Key Laboratory of Membrane Biology,Institute of Zoology, Institute for Stem Cell and Regeneration Chinese Academy of Sciences, University of Chinese Academy of Sciences 100101 Beijing ChinaThe First Affiliated Hospital The Second Affiliated Hospital Institute of Translational Medicine School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine 310058 Hangzhou ChinaThe First Affiliated Hospital The Second Affiliated Hospital Institute of Translational Medicine School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine 310058 Hangzhou ChinaThe First Affiliated Hospital The Second Affiliated Hospital Institute of Translational Medicine School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine 310058 Hangzhou ChinaThe First Affiliated Hospital The Second Affiliated Hospital Institute of Translational Medicine School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine 310058 Hangzhou ChinaThe First Affiliated Hospital The Second Affiliated Hospital Institute of Translational Medicine School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine 310058 Hangzhou ChinaWomen's Hospital, and Institute of Genetics Zhejiang University School of Medicine Hangzhou Zhejiang 310058 ChinaWomen's Hospital, and Institute of Genetics Zhejiang University School of Medicine Hangzhou Zhejiang 310058 ChinaThe First Affiliated Hospital The Second Affiliated Hospital Institute of Translational Medicine School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine 310058 Hangzhou ChinaThe First Affiliated Hospital The Second Affiliated Hospital Institute of Translational Medicine School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine 310058 Hangzhou ChinaAbstract 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.https://doi.org/10.1002/advs.202205345anemiahematopoiesishematopoietic stem cellsHSPCsSLC39A10zinc homeostasis |
| spellingShingle | Xuyan He Chaodong Ge Jun Xia Zhidan Xia Lu Zhao Sicong Huang Rong Wang Jianwei Pan Tao Cheng Peng‐Fei Xu Fudi Wang Junxia Min The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis Advanced Science anemia hematopoiesis hematopoietic stem cells HSPCs SLC39A10 zinc homeostasis |
| 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 | anemia hematopoiesis hematopoietic stem cells HSPCs SLC39A10 zinc homeostasis |
| url | https://doi.org/10.1002/advs.202205345 |
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