دورية أكاديمية
The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis
العنوان: | The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis |
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المؤلفون: | 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 |
المصدر: | Advanced Science, Vol 10, Iss 17, Pp n/a-n/a (2023) |
بيانات النشر: | Wiley, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Science |
مصطلحات موضوعية: | anemia, hematopoiesis, hematopoietic stem cells, HSPCs, SLC39A10, zinc homeostasis, Science |
الوصف: | 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. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2198-3844 29041880 |
Relation: | https://doaj.org/toc/2198-3844 |
DOI: | 10.1002/advs.202205345 |
URL الوصول: | https://doaj.org/article/9be81e22e2804831afed8a29041880d8 |
رقم الأكسشن: | edsdoj.9be81e22e2804831afed8a29041880d8 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 21983844 29041880 |
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DOI: | 10.1002/advs.202205345 |