文献类型：期刊文献

英文题名：Ikzf1 regulates embryonic T lymphopoiesis via Ccr9 and Irf4 in zebrafish

作者：Huang, Youkui[1];Lu, Yafang[1];He, Yuepeng[1];Feng, Zhi[1];Zhan, Yandong[1];Huang, Xue[1];Liu, Qin[2];Zhang, Jingjing[3];Li, Hongtao[1];Huang, Honghui[1];Ma, Ming[1];Luo, Lingfei[1];Li, Li[1]

机构：[1]Southwest Univ, Key Lab Aquat Sci Chongqing, Lab Mol Dev Biol,Minist Educ, Key Lab Freshwater Fish Reprod & Dev,Sch Life Sci, Chongqing 400715, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Guangzhou Med Univ, Affiliated Hosp, Zhanjiang 524001, Guangdong, Peoples R China

年份：2019

卷号：294

期号：44

起止页码：16152

外文期刊名：JOURNAL OF BIOLOGICAL CHEMISTRY

收录：;EI(收录号：20194507642521);WOS:【SCI-EXPANDED(收录号:WOS:000499478600023)】；

基金：This work was supported by National Natural Science Foundation of China Grants 31822033, 31771623, 31571500, and 31771628); National Key Basic Research Program of China Grant 2015CB942802; and Fundamental Research Funds for the Central Universities Grant XDJK2017A015 and partially supported by an open funding project of the State Key Laboratory of Bioreactor Engineering and Guangdong Natural Science Fund for Distinguished Young Scholars (2017A030306024). The authors declare that they have no conflicts of interest with the contents of this article.

语种：英文

外文关键词：lymphocyte; development; transcription factor; migration; zebrafish

摘要：Ikzf1 is a Kr?ppel-like zinc-finger transcription factor that plays indispensable roles in T and B cell development. Although the function of Ikzf1 has been studied extensively, the molecular mechanism underlying T lymphopoiesis remains incompletely defined during the embryonic stage. Here we report that the genetic ablation of ikzf1 in mutant zebrafish resulted in abrogated embryonic T lymphopoiesis. This was ascribed to impaired thymic migration, proliferation, and differentiation of hematopoietic stem/progenitor cells (HSPCs). Ccr9a and Irf4a, two indispensable factors in T lymphopoiesis, were the direct targets of Ikzf1 and were absent in the ikzf1 mutants. Genetic deletion of either ccr9a or irf4a in the corresponding mutant embryos led to obvious T cell development deficiency, which was mainly caused by disrupted thymic migration of HSPCs. Restoration of ccr9a in ikzf1 mutants obviously promoted HSPC thymus homing. However, the HSPCs then failed to differentiate into T cells. Additional replenishment of irf4a efficiently induced HSPC proliferation and T cell differentiation. Our findings further demonstrate that Ikzf1 regulates embryonic T lymphopoiesis via Ccr9 and Irf4 and provide new insight into the genetic network of T lymphocyte development.