| 论文题目： | Thyroid Hormone Regulates Hematopoiesis via the TR-KLF9 Axis |
| 论文题目英文： | |
| 作者： | 张颖①，薛媛媛①，曹春伟①，黄娇娇，洪潜龙，海棠，贾启涛，王宪龙，秦国嵩，姚婧，王霄，郑千涛，张蕊，Yong-Shun Li，罗霭玲，张楠，#Gui-Zhi Shi，#王彦芳，#Hao Ying，#刘忠华，王红梅，#孟安明，周琪，#魏泓*，刘峰*，赵建国* |
| 论文出处： | |
| 年： | 2017 |
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| 期： | DOI: 10.1182/blood-2017-05-783043 |
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| 联系作者： | #魏泓，刘峰，赵建国 |
| 发表期刊： | Blood |
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| 论文连接 | http://www.bloodjournal.org/content/early/2017/09/22/blood-2017-05-783043?sso-checked=true |
| 影响因子： | |
| 摘要: | Congenital hypothyroidism (CH) is one of the most prevalent endocrine diseases and is often accompanied by anemia and immunodeficiency in patients, for which the underlying mechanisms remain unknown. Here we created a severe CH model together with anemia and T lymphopenia to mimic the clinical features of hypothyroid patients by ethylnitrosourea (ENU) mutagenesis in Bama miniature pigs. A novel recessive c.1226A>G transition of the dual oxidase 2 (DUOX2) gene was identified as the causative mutation. This mutation hindered the production of hydrogen peroxide (H2O2) and thus contributed to thyroid hormone (TH) synthesis failure. Transcriptome sequencing analysis of the thymuses showed that Krüppel-like factor 9 (KLF9) was predominantly down-regulated in hypothyroid mutants. KLF9 was verified to be directly regulated by TH in a TH receptor (TR)-dependent manner both in vivo and in vitro. Furthermore, knockdown of klf9 in zebrafish embryos impaired hematopoietic development including erythroid maturation and T lymphopoiesis. Our findings suggest that the TR-KLF9 axis is responsible for the hematopoietic dysfunction and might be exploited for the development of novel therapeutic interventions for thyroid diseases. |
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