CFTR regulates embryonic T lymphopoiesis via Wnt signaling in zebrafish

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.