NR2F2 Regulates Cell Proliferation and Immunomodulation in Whartons’ Jelly Stem Cells

(1) Background: Wharton’s Jelly stem cells (WJ-MSCs) are multipotent mesenchymal stem cells that can proliferate rapidly and have low immunogenicity. Therefore, WJ-MSCs have gained considerable attention in the fields of immunomodulation and disease treatment and have entered clinical trials for the...

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Main Authors: Li Ma, Min Huang, Xiaohua Liao, Xiyu Cai, Qiang Wu
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Genes
Subjects:
Online Access:https://www.mdpi.com/2073-4425/13/8/1458
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author Li Ma
Min Huang
Xiaohua Liao
Xiyu Cai
Qiang Wu
author_facet Li Ma
Min Huang
Xiaohua Liao
Xiyu Cai
Qiang Wu
author_sort Li Ma
collection DOAJ
description (1) Background: Wharton’s Jelly stem cells (WJ-MSCs) are multipotent mesenchymal stem cells that can proliferate rapidly and have low immunogenicity. Therefore, WJ-MSCs have gained considerable attention in the fields of immunomodulation and disease treatment and have entered clinical trials for the treatment of various diseases. Therefore, it is crucial to study the underlying mechanisms of WJ-MSCs proliferation, immune regulation, and disease treatment. Nuclear Receptor Subfamily 2 Group F Member 2 (NR2F2) is a transcription factor that is involved in the regulation of many different genes. However, it remains unknown how NR2F2 regulates stem cell identity in WJ-MSCs. (2) Methods: We used RNAi technology to knock down NR2F2 in WJ-MSCs, and studied the regulatory role of NR2F2 in WJ-MSCs by MTT, flow cytometry, RNA-seq, and other methods. We also utilized a co-culture system in which NR2F2-depleted WJ-MSCs with MH7A and HCT116/HepG2 were used to investigate the role of NR2F2 in immunomodulation and the inhibition of cancer cell growth. (3) Results: NR2F2 knockdown resulted in decreased expressions of Cyclin D1 and CDK4, slower cell proliferation, and increased expressions of IL6 and IL8. Furthermore, Cyclin D1, CDK4, and inflammatory factors were increased in human rheumatoid fibroblast-like synoviocyte line MH7A if co-cultured with NR2F2 depleted WJ-MSCs. In addition, we observed increased p53, decreased BCL-2, and increased cell apoptosis in liver cancer cell line HepG2 if co-cultured with NR2F2-depleted WJ-MSCs. (4) Conclusions: NR2F2 not only plays an important role in the cell cycle and immune regulation of WJ-MSCs but also has potential effects on the WJ-MSCs treatment of related diseases.
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spelling doaj.art-0df80fd636f24de0a8fe51c5d89d13572023-12-01T23:44:29ZengMDPI AGGenes2073-44252022-08-01138145810.3390/genes13081458NR2F2 Regulates Cell Proliferation and Immunomodulation in Whartons’ Jelly Stem CellsLi Ma0Min Huang1Xiaohua Liao2Xiyu Cai3Qiang Wu4The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999087, ChinaThe State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999087, ChinaThe State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999087, ChinaDepartment of Orthopedic, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, ChinaThe State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999087, China(1) Background: Wharton’s Jelly stem cells (WJ-MSCs) are multipotent mesenchymal stem cells that can proliferate rapidly and have low immunogenicity. Therefore, WJ-MSCs have gained considerable attention in the fields of immunomodulation and disease treatment and have entered clinical trials for the treatment of various diseases. Therefore, it is crucial to study the underlying mechanisms of WJ-MSCs proliferation, immune regulation, and disease treatment. Nuclear Receptor Subfamily 2 Group F Member 2 (NR2F2) is a transcription factor that is involved in the regulation of many different genes. However, it remains unknown how NR2F2 regulates stem cell identity in WJ-MSCs. (2) Methods: We used RNAi technology to knock down NR2F2 in WJ-MSCs, and studied the regulatory role of NR2F2 in WJ-MSCs by MTT, flow cytometry, RNA-seq, and other methods. We also utilized a co-culture system in which NR2F2-depleted WJ-MSCs with MH7A and HCT116/HepG2 were used to investigate the role of NR2F2 in immunomodulation and the inhibition of cancer cell growth. (3) Results: NR2F2 knockdown resulted in decreased expressions of Cyclin D1 and CDK4, slower cell proliferation, and increased expressions of IL6 and IL8. Furthermore, Cyclin D1, CDK4, and inflammatory factors were increased in human rheumatoid fibroblast-like synoviocyte line MH7A if co-cultured with NR2F2 depleted WJ-MSCs. In addition, we observed increased p53, decreased BCL-2, and increased cell apoptosis in liver cancer cell line HepG2 if co-cultured with NR2F2-depleted WJ-MSCs. (4) Conclusions: NR2F2 not only plays an important role in the cell cycle and immune regulation of WJ-MSCs but also has potential effects on the WJ-MSCs treatment of related diseases.https://www.mdpi.com/2073-4425/13/8/1458WJ-MSCsNR2F2RNA-seqgene regulatory networkcell cycleimmunomodulation
spellingShingle Li Ma
Min Huang
Xiaohua Liao
Xiyu Cai
Qiang Wu
NR2F2 Regulates Cell Proliferation and Immunomodulation in Whartons’ Jelly Stem Cells
Genes
WJ-MSCs
NR2F2
RNA-seq
gene regulatory network
cell cycle
immunomodulation
title NR2F2 Regulates Cell Proliferation and Immunomodulation in Whartons’ Jelly Stem Cells
title_full NR2F2 Regulates Cell Proliferation and Immunomodulation in Whartons’ Jelly Stem Cells
title_fullStr NR2F2 Regulates Cell Proliferation and Immunomodulation in Whartons’ Jelly Stem Cells
title_full_unstemmed NR2F2 Regulates Cell Proliferation and Immunomodulation in Whartons’ Jelly Stem Cells
title_short NR2F2 Regulates Cell Proliferation and Immunomodulation in Whartons’ Jelly Stem Cells
title_sort nr2f2 regulates cell proliferation and immunomodulation in whartons jelly stem cells
topic WJ-MSCs
NR2F2
RNA-seq
gene regulatory network
cell cycle
immunomodulation
url https://www.mdpi.com/2073-4425/13/8/1458
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