Inhibition of Tet1- and Tet2-mediated DNA demethylation promotes immunomodulation of periodontal ligament stem cells

Yu, Tingting; Liu, Dawei; Zhang, Ting; Zhou, Yan-Heng; Shi, Songtao; Yang, Ruili

doi:10.1038/s41419-019-2025-z

Cited by 29 publications

(31 citation statements)

References 43 publications

(57 reference statements)

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“…Recently, different biological therapies have been reported and demonstrated superior efficacy and safety 24 . It has been reported that MSCs derived from different tissues such as bone marrow MSCs 25 , MSC from periodontal ligament 26 , and MSC from adipose tissue 27 could alleviate colitis. However, some researcher raised the concerns about the fate of stem cells infused to body.…”

Section: Discussionmentioning

confidence: 99%

“…For analysis of exosomes, exosome protein was isolated from the culture supernatant of 4 × 10 6 cells, and 10 μg of total exosome proteins was loaded. For western analysis of cells, the 10 μg proteins were loaded for western blot as per our previously described report 26 . The relative density was measured using ImageJ 1.49v software (Wayne Rasband).…”

Section: Discussionmentioning

confidence: 99%

“…To analyze the expression of mRNA, SuperScript III Reverse Transcriptase (RT) kit (Invitrogen) was used to synthesis cDNA. qPCR was performed using the specific primer (listed in Table S2 ) as previously described 26 . The level of mRNA expression was normalized to glyceraldehyde 3-phosphate dehydrogenase.…”

Section: Discussionmentioning

confidence: 99%

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IFN-γ promoted exosomes from mesenchymal stem cells to attenuate colitis via miR-125a and miR-125b

et al. 2020

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Bone marrow mesenchymal stem cells (MSCs) have demonstrated therapeutic effects for colitis through immunomodulation and anti-inflammation. However, whether MSC-derived exosomes possessed the similar function remains unclear. In present study, exosomes were isolated from control and IFN-γ-primed MSCs and was verified by transmission electron microscope (TEM) and immunofluorescence staining. Administration of exosomes to mice significantly improved the disease activity index and histological score of colitis, and decreased the ratio of Th17 cells with elevated Treg cells ratio in mice colitis model. Exosomes from IFN-γ-primed MSCs showed superior therapeutic effects to colitis. Exosomes treatment inhibited Th17 differentiation in vitro, and exosomes from IFN-γ-primed MSCs showed higher inhibition efficacy. Mechanistically, exosomes treatment significantly decreased the expression of Stat3 and p-Stat3 to inhibit Th17 cells differentiation. IFN-γ pretreatment increased the level of miR-125a and miR-125b of exosomes, which directly targeted on Stat3, to repress Th17 cell differentiation. Moreover, combination of miR-125a and miR-125b agmior infusion also showed therapeutic effects for colitis, accompanied by decreased Th17 cell ratio. Collectively, this study demonstrates that IFN-γ treatment promoted exosomes from MSCs to attenuate colitis through increasing the level of miR-125a and miR-125b, which binding on 3′-UTR of Stat3 to repress Th17 cell differentiation. This study provides a new approach of exocytosis on the treatment of colitis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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IFN-γ promoted exosomes from mesenchymal stem cells to attenuate colitis via miR-125a and miR-125b

et al. 2020

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“…Loss of Tet1 and Tet2 led to a hypermethylated Dkk-1 promoter, which induces Wnt/β-catenin signaling and Fasligand expression. 220 In addition, MSCs have been shown to convert conventional T lymphocytes into iTreg cells. 221 Posttranslational stability of Foxp3, through ubiquitin modifications, determines immunosuppressive function of iTreg cells.…”

Section: Regulation In Immunit Ymentioning

confidence: 99%

Emerging trends in chromatin remodeler plasticity in mesenchymal stromal cell function

2020

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Emerging evidences highlight importance of epigenetic regulation and their integration with transcriptional and cell signaling machinery in determining tissue resident adult pluripotent mesenchymal stem/stromal cell (MSC) activity, lineage commitment, and multicellular development. Histone modifying enzymes and large multi‐subunit chromatin remodeling complexes and their cell type‐specific plasticity remain the central defining features of gene regulation and establishment of tissue identity. Modulation of transcription factor expression gradient ex vivo and concomitant flexibility of higher order chromatin architecture in response to signaling cues are exciting approaches to regulate MSC activity and tissue rejuvenation. Being an important constituent of the adult bone marrow microenvironment/niche, pathophysiological perturbation in MSC homeostasis also causes impaired hematopoietic stem/progenitor cell function in a non‐cell autonomous mechanism. In addition, pluripotent MSCs can function as immune regulatory cells, and they reside at the crossroad of innate and adaptive immune response pathways. Research in the past few years suggest that MSCs/stromal fibroblasts significantly contribute to the establishment of immunosuppressive microenvironment in shaping antitumor immunity. Therefore, it is important to understand mesenchymal stromal epigenome and transcriptional regulation to leverage its applications in regenerative medicine, epigenetic memory‐guided trained immunity, immune‐metabolic rewiring, and precision immune reprogramming. In this review, we highlight the latest developments and prospects in chromatin biology in determining MSC function in the context of lineage commitment and immunomodulation.

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“…Previous studies reported that the TET protein family, which includes important enzymes of DNA demethylation, is regulated by O-glycosylation, and plays an important role in maintaining the stemness of stem cells (Zhang et al, 2014;Hahn et al, 2019;Ross and Bogdanovic, 2019;Yu et al, 2019). The dynamic protein levels of TET were investigated by electrochemical techniques because of their high sensitivity, low instrumentation cost, relatively shorter analysis times, and lack of tedious extraction procedures when compared with other analytical techniques (Pandit et al, 2017).…”

Section: Dynamic Tet Analyzed In Mammalian Oogenesis and Preimplantatmentioning

confidence: 99%

Integrated Glycosylation Patterns of Glycoproteins and DNA Methylation Landscapes in Mammalian Oogenesis and Preimplantation Embryo Development

Wang

Tian

et al. 2020

Front. Cell Dev. Biol.

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Glycosylation is one of the most fundamental post-translational modifications. However, the glycosylation patterns of glycoproteins have not been analyzed in mammalian preimplantation embryos, because of technical difficulties and scarcity of the required materials. Using high-throughput lectin microarrays of low-input cells and electrochemical techniques, an integration analysis of the DNA methylation and glycosylation landscapes of mammal oogenesis and preimplantation embryo development was performed. Highly noticeable changes occurred in the level of protein glycosylation during these events. Further analysis identified several stagespecific lectins including LEL, MNA-M, and MAL I. It was later confirmed that LEL was involved in mammalian oogenesis and preimplantation embryogenesis, and might be a marker of FGSC differentiation. Modified nanocomposite polyaniline/AuNPs were characterized by electron microscopy and modification on bare gold electrodes using layer-by-layer assembly technology. These nanoparticles were further subjected to accuracy measurements by analyzing the protein level of ten-eleven translocation protein (TET), which is an important enzyme in DNA demethylation that is regulated by O-glycosylation. Subsequent results showed that the variations in the glycosylation patterns of glycoproteins were opposite to those of the TET levels. Moreover, analysis of correlation between the changes in glyco-gene expression and female germline stem cell glycosylation profiles indicated that glycosylation was related to DNA methylation. Subsequent integration analysis showed that the trend in the variations of glycosylation patterns of glycoproteins was similar to that of DNA methylation and opposite to that of the TET protein levels during female germ cell and preimplantation embryo development. Our findings provide insight into the complex molecular mechanisms that regulate human embryo development, and a foundation for further elucidation of early embryonic development and informed reproductive medicine.

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Inhibition of Tet1- and Tet2-mediated DNA demethylation promotes immunomodulation of periodontal ligament stem cells

Cited by 29 publications

References 43 publications

IFN-γ promoted exosomes from mesenchymal stem cells to attenuate colitis via miR-125a and miR-125b

IFN-γ promoted exosomes from mesenchymal stem cells to attenuate colitis via miR-125a and miR-125b

Emerging trends in chromatin remodeler plasticity in mesenchymal stromal cell function

Integrated Glycosylation Patterns of Glycoproteins and DNA Methylation Landscapes in Mammalian Oogenesis and Preimplantation Embryo Development

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