CFTR regulates embryonic T lymphopoiesis via Wnt signaling in zebrafish
CFTR regulates embryonic T lymphopoiesis via Wnt signaling in zebrafish
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DOI：
10.1016/j.imlet.2021.04.010
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发表时间：
2021-05-11
影响因子：
4.4
通讯作者：
Sun, Huaqin
中科院分区：
文献类型：
--
作者：
Lin, Ziyuan;Luo, Min;Sun, Huaqin
如在囊性纤维化（CF）患者和CF小鼠模型中观察到的，T细胞的数量和功能异常，并且我们先前的工作表明CFTR突变导致斑马鱼中原始造血和定型造血的缺乏。然而，CFTR在早期胚胎发育过程中T细胞发育中的功能和潜在机制尚未被探索。在这里，我们报告说，在斑马鱼CFTR的基因消融导致废除胚胎T淋巴细胞生成，这是由于受损的胸腺归巢和造血干细胞（HSC）的扩增。在48 hpf的斑马鱼胚胎中分离的HSC的转录组分析显示T细胞发育和Wnt信号传导所必需的关键因子的显著改变，与我们先前关于CFTR调节造血的工作一致。总之，我们揭示了CFTR在胚胎T细胞发育中的功能，并表明CF患者的免疫缺陷可能起源于早期胚胎阶段。
The number and function of T cells are abnormal as observed in cystic fibrosis (CF) patients and CF mouse models, and our previous work shows that the CFTR mutant leads to deficiency of primitive and definitive hematopoietic in zebrafish. However, the functions and underlying mechanisms of CFTR in T cell development during early embryogenesis have not been explored. Here, we report that the genetic ablation of CFTR in zebrafish resulted in abrogated embryonic T lymphopoiesis, which was ascribed to impaired thymic homing and expansion of hematopoietic stem cells (HSCs). Transcriptome analysis of isolated HSCs in zebrafish embryos at 48 hpf showed a significant alteration of key factors essential for T cell development and Wnt signaling, consistent with our previous work on CFTR regulating hematopoiesis. In brief, we uncovered the function of CFTR in embryonic T cell development and suggest that the immune deficiency of CF patients may originate from an early embryonic stage.