CFTR regulates embryonic T lymphopoiesis via Wnt signaling in zebrafish

Ziyuan Lin; Min Luo; Bin Zhou; Yanyan Liu; Huaqin Sun

doi:10.1016/j.imlet.2021.04.010

CFTR regulates embryonic T lymphopoiesis via Wnt signaling in zebrafish

Immunol Lett. 2021 Jun:234:47-53. doi: 10.1016/j.imlet.2021.04.010. Epub 2021 May 2.

Authors

Ziyuan Lin¹, Min Luo², Bin Zhou³, Yanyan Liu⁴, Huaqin Sun⁵

Affiliations

¹ SCU-CUHK Joint Laboratory for Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, PR China.
² Prenatal Diagnosis Center, Department of Obstetrics & Gynecologic, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, PR China.
³ Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, PR China.
⁴ Prenatal Diagnosis Center, Department of Obstetrics & Gynecologic, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: liuyy39@qq.com.
⁵ SCU-CUHK Joint Laboratory for Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: sunhuaqin@scu.edu.cn.

PMID: 33951474
DOI: 10.1016/j.imlet.2021.04.010

Abstract

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.

Keywords: CFTR; T lymphopoiesis; Wnt signaling; zebrafish.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / genetics*
Computational Biology / methods
Cystic Fibrosis Transmembrane Conductance Regulator / genetics
Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
Disease Models, Animal
Gene Expression Profiling
Gene Expression Regulation, Developmental*
Gene Ontology
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / metabolism
Lymphopoiesis / genetics*
Mutation
Phenotype
T-Lymphocytes / cytology*
T-Lymphocytes / metabolism*
Wnt Signaling Pathway*
Zebrafish

Substances

Cystic Fibrosis Transmembrane Conductance Regulator