ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation (2024)

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Cells

Volume 13

Issue 12

10.3390/cells13121073

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Article

by

Tzong-Shyuan Tai

ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation (5)Tzong-Shyuan Tai

1,

Huang-Yu Yang

2,3,4,

Wan-Chu Chuang

5,

Yu-Wen Huang

5ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation (9),

I-Cheng Ho

6,7,

Ching-Chung Tsai

ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation (11)Ching-Chung Tsai

8,9,*ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation (12) and

Ya-Ting Chuang

5,*

1

Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan

2

Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan

3

College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan

4

Advanced Immunology Laboratory, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan

5

Department of Medical Research, National Taiwan University Hospital, Taipei 10002, Taiwan

6

Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital, 60 Fenwood Road, Boston, MA 02115, USA

7

Harvard Medical School, 60 Fenwood Road, Boston, MA 02115, USA

8

Department of Pediatrics, E-Da Hospital, I-Shou University, Kaohsiung City 82445, Taiwan

9

School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung City 82445, Taiwan

*

Authors to whom correspondence should be addressed.

Cells 2024, 13(12), 1073; https://doi.org/10.3390/cells13121073

Submission received: 21 May 2024 / Revised: 18 June 2024 / Accepted: 19 June 2024 / Published: 20 June 2024

(This article belongs to the Collection Feature Papers in ‘Cellular Immunology’)

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Abstract

While the transcription factor GATA-3 is well-established for its crucial role in T cell development, its specific influence on invariant natural killer T (iNKT) cells remains relatively unexplored. Using flow cytometry and single-cell transcriptomic analysis, we demonstrated that GATA-3 deficiency in mice leads to the absence of iNKT2 and iNKT17 cell subsets, as well as an altered distribution of iNKT1 cells. Thymic iNKT cells lacking GATA-3 exhibited diminished expression of PLZF and T-bet, key transcription factors involved in iNKT cell differentiation, and reduced production of Th2, Th17, and cytotoxic effector molecules. Single-cell transcriptomics revealed a comprehensive absence of iNKT17 cells, a substantial reduction in iNKT2 cells, and an increase in iNKT1 cells in GATA-3-deficient thymi. Differential expression analysis highlighted the regulatory role of GATA-3 in T cell activation signaling and altered expression of genes critical for iNKT cell differentiation, such as Icos, Cd127, Eomes, and Zbtb16. Notably, restoration of Icos, but not Cd127, expression could rescue iNKT cell development in GATA-3-deficient mice. In conclusion, our study demonstrates the pivotal role of GATA-3 in orchestrating iNKT cell effector lineage differentiation through the regulation of T cell activation pathways and Icos expression, providing insights into the molecular mechanisms governing iNKT cell development and function.

Keywords: iNKT cells; single-cell RNA sequencing; GATA-3; Icos; CD127

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MDPI and ACS Style

Tai, T.-S.; Yang, H.-Y.; Chuang, W.-C.; Huang, Y.-W.; Ho, I.-C.; Tsai, C.-C.; Chuang, Y.-T. ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation. Cells 2024, 13, 1073. https://doi.org/10.3390/cells13121073

AMA Style

Tai T-S, Yang H-Y, Chuang W-C, Huang Y-W, Ho I-C, Tsai C-C, Chuang Y-T. ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation. Cells. 2024; 13(12):1073. https://doi.org/10.3390/cells13121073

Chicago/Turabian Style

Tai, Tzong-Shyuan, Huang-Yu Yang, Wan-Chu Chuang, Yu-Wen Huang, I-Cheng Ho, Ching-Chung Tsai, and Ya-Ting Chuang. 2024. "ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation" Cells 13, no. 12: 1073. https://doi.org/10.3390/cells13121073

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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MDPI and ACS Style

Tai, T.-S.; Yang, H.-Y.; Chuang, W.-C.; Huang, Y.-W.; Ho, I.-C.; Tsai, C.-C.; Chuang, Y.-T. ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation. Cells 2024, 13, 1073. https://doi.org/10.3390/cells13121073

AMA Style

Tai T-S, Yang H-Y, Chuang W-C, Huang Y-W, Ho I-C, Tsai C-C, Chuang Y-T. ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation. Cells. 2024; 13(12):1073. https://doi.org/10.3390/cells13121073

Chicago/Turabian Style

Tai, Tzong-Shyuan, Huang-Yu Yang, Wan-Chu Chuang, Yu-Wen Huang, I-Cheng Ho, Ching-Chung Tsai, and Ya-Ting Chuang. 2024. "ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation" Cells 13, no. 12: 1073. https://doi.org/10.3390/cells13121073

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation (14)

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