PUBLICATION

CFTR regulates embryonic T lymphopoiesis via Wnt signaling in zebrafish

Authors

Lin, Z., Luo, M., Zhou, B., Liu, Y., Sun, H.

ID

ZDB-PUB-210506-7

Date

2021

Source

Immunology Letters 234: 47-53 (Journal)

Registered Authors

Sun, Huaqin

Keywords

CFTR, T lymphopoiesis, Wnt signaling, Zebrafish

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

(all 18)

PubMed

33951474 Full text @ Immunol. Lett.

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.

Genes / Markers

Marker	Marker Type	Name
cacna1fb	GENE	calcium channel, voltage-dependent, L type, alpha 1F subunit
ccl25a	GENE	chemokine (C-C motif) ligand 25a
ccr9a	GENE	chemokine (C-C motif) receptor 9a
cd83	GENE	CD83 molecule
cdh15	GENE	cadherin 15, type 1, M-cadherin (myotubule)
cdh17	GENE	cadherin 17, LI cadherin (liver-intestine)
cftr	GENE	CF transmembrane conductance regulator
coro1a	GENE	coronin, actin binding protein, 1A
csf1ra	GENE	colony stimulating factor 1 receptor, a
foxc1a	GENE	forkhead box C1a

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Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
cftr^{scu102/scu102}	standard conditions	Prim-5	macrophage csf1ra expression decreased amount, abnormal	Fig. S2
cftr^{scu102/scu102}	standard conditions	Prim-5	neutrophil mpx expression decreased amount, abnormal	Fig. S2
cftr^{scu102/scu102}	standard conditions	Day 4	thymic epithelium ccl25a expression decreased amount, abnormal	Fig. 1
cftr^{scu102/scu102}	standard conditions	Day 4	thymic epithelium foxn1 expression decreased amount, abnormal	Fig. 1
cftr^{scu102/scu102}	standard conditions	Day 4	thymus ccr9a expression decreased amount, abnormal	Fig. 1
cftr^{scu102/scu102}	standard conditions	Day 4	thymus rag1 expression decreased amount, abnormal	Fig. 1
cftr^{scu102/scu102}	standard conditions	Day 4	thymus rag2 expression decreased amount, abnormal	Fig. 1
cftr^{scu102/scu102}	standard conditions	Day 6	thymus rag1 expression decreased amount, abnormal	Fig. S1
cftr^{scu102/scu102}	standard conditions	Days 7-13	thymus rag1 expression decreased amount, abnormal	Fig. S1
cftr^{scu102/scu102}; zf169Tg	standard conditions	Long-pec	hematopoietic stem cell cacna1fb expression increased amount, abnormal	Fig. 3

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
hkz04tTg	Tg(coro1a:EGFP)	Transgenic Insertion
la2Tg	Tg(-6.0itga2b:EGFP)	Transgenic Insertion
nz50Tg	Tg(lyz:DsRed2)	Transgenic Insertion
scu102		Small Deletion	cftr
zf169Tg	TgPAC(myb:2xmyb-EGFP)	Transgenic Insertion

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Human Disease / Model

Human Disease	Fish	Conditions	Evidence
cystic fibrosis			TAS

Sequence Targeting Reagents

Fish

Fish
cftr^{scu102/scu102}
cftr^{scu102/scu102}; hkz04tTg
cftr^{scu102/scu102}; zf169Tg

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
DsRed2	EFG	DsRed2
EGFP	EFG	EGFP

Mapping

Lin et al., 2021 ZDB-PUB-210506-7 PMID:33951474

CFTR regulates embryonic T lymphopoiesis via Wnt signaling in zebrafish

Lin et al., 2021

ZDB-PUB-210506-7
PMID:33951474