101. Ikzf1 regulates embryonic T lymphopoiesis via Ccr9 and Irf4 in zebrafish
- Author
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Honghui Huang, Xue Huang, Ming Ma, Yuepeng He, Hongtao Li, Yafang Lu, Jingjing Zhang, Lingfei Luo, Li Li, Youkui Huang, Zhi Feng, Yandong Zhan, and Qin Liu
- Subjects
0301 basic medicine ,Lymphocyte ,T cell ,T-Lymphocytes ,Biology ,Biochemistry ,03 medical and health sciences ,Ikaros Transcription Factor ,Receptors, CCR ,medicine ,Animals ,Gene Regulatory Networks ,Lymphopoiesis ,Progenitor cell ,Molecular Biology ,B cell ,Zebrafish ,Cell Proliferation ,030102 biochemistry & molecular biology ,Cell Differentiation ,Cell Biology ,T lymphocyte ,Zebrafish Proteins ,Hematopoietic Stem Cells ,Embryonic stem cell ,Cell biology ,Hematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,T cell differentiation ,Interferon Regulatory Factors ,Mutation ,Developmental Biology - Abstract
Ikzf1 is a Kruppel-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.
- Published
- 2019