The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis.
The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis.
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DOI：
10.1002/advs.202205345
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发表时间：
2023-06
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影响因子：
--
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中科院分区：
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锌在造血中的作用目前尚不清楚。在这里，SLC 39 A10（ZIP 10）被确定为造血中的关键锌转运蛋白。结果表明，在斑马鱼中，Slc 39 a10是锌缺乏反应的关键调节因子。令人惊讶的是，slc 39 a10突变斑马鱼和造血Slc 39 a10缺陷小鼠的造血功能受损形式比缺乏转铁蛋白受体1（一种特征良好的铁守门人）的动物更严重，表明锌在造血中发挥的作用比铁更大，至少在早期造血干细胞（HSC）中。此外，研究表明，Slc 39 a10的缺失导致胎儿HSC中锌缺乏，这反过来又导致DNA损伤、凋亡和G1细胞周期停滞。值得注意的是，锌补充在很大程度上恢复造血Slc 39 a10缺陷小鼠来源的HSC中的集落形成。此外，抑制坏死性凋亡可部分恢复小鼠HSC中的造血功能，从而为锌在介导造血功能中的需求提供了机制性见解。总之，这些研究结果表明，SLC 39 A10通过防止锌缺乏诱导的坏死性凋亡来保护造血，从而提供了令人信服的证据，表明SLC 39 A10和锌稳态促进胎儿HSC的发育。此外，这些结果表明，SLC 39 A10可以作为治疗贫血和缺锌相关疾病的新的治疗靶点。 Slc 39 a10（Zip 10）作为锌转运蛋白，在斑马鱼和小鼠胚胎造血干/祖细胞的存活中起重要作用。Slc 39 a10的缺失导致造血功能受损，可以通过补充锌或抑制坏死性凋亡来挽救。这项研究表明，Slc 39 a10通过维持锌稳态促进胎儿造血干细胞的发育。
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. Slc39a10 (Zip10), as a zinc transporter, plays an essential role in the survival of fetal hematopoietic stem/progenitor cells in both zebrafish and mice. Loss of Slc39a10 causes impaired hematopoiesis that can be rescued by zinc supplementation or inhibiting necroptosis. This study shows that Slc39a10 promotes the development of fetal hematopoietic stem cells by maintaining zinc homeostasis.
Slc39a5介导的锌稳态在斑马鱼静脉血管生成中发挥重要作用
影响因子：
5.8
作者：
Xia Z;Bi X;Lian J;Dai W;He X;Zhao L;Min J;Wang F
通讯作者：
Wang F