STAT3-Inducible Mouse ESCs: A Model to Study the Role of STAT3 in ESC Maintenance and Lineage Differentiation

Wong, Yu Qian; Xu, Hongyan; Wu, Qiang; Liu, Xin Yu; Lufei, Chengchen; Xiao-hong, XU; Fu, Xin-Yuan

doi:10.1155/2018/8632950

Cited by 6 publications

(7 citation statements)

References 90 publications

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“…A remaining question is the molecular mechanisms through which TNFR2 mediates CSC proliferation, differentiation and maturation. Recent studies suggest that both Akt and STAT3 are critical for CSC proliferation and differentiation from ESCs. We observe that both Akt and STAT3 are highly activated at early phase of CSC differentiation.…”

Section: Discussionsupporting

confidence: 48%

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Critical role of Lin28‐TNFR2 signalling in cardiac stem cell activation and differentiation

Qiu

Yang

et al. 2019

J Cellular Molecular Medi

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Tumour necrotic factor receptor‐2 (TNFR2) has been to be cardiac‐protective and is expressed in cardiac progenitor cells. Our goal is to define the mechanism for TNFR2‐mediated cardiac stem cell activation and differentiation. By employing a protocol of in vitro cardiac stem cell (CSC) differentiation from human inducible pluripotent stem cell (hiPSC), we show that expression of TNFR2 precedes expression of CSC markers followed by expression of mature cardiomyocyte proteins. Activation of TNFR2 by a specific agonist promotes whereas inhibition of TNFR2 by neutralizing antibody diminishes hiPSC‐based CSC differentiation. Interestingly, pluripotent cell factor RNA‐binding protein Lin28 enhances TNFR2 protein expression in early CSC activation by directly binding to a conserved Lin28‐motif within the 3'UTR of Tnfr2 mRNA. Furthermore, inhibition of Lin28 blunts TNFR2 expression and TNFR2‐dependent CSC activation and differentiation. Our study demonstrates a critical role of Lin28‐TNFR2 axis in CSC activation and survival, providing a novel strategy to enhance stem cell‐based therapy for the ischaemic heart diseases.

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Section: Discussionsupporting

confidence: 48%

“…Recent studies suggest that both Akt and STAT3 are critical for CSC proliferation and differentiation from ESCs 41,42 . We observe that both Akt and STAT3 are highly activated at early phase of CSC differentiation.…”

Section: Discussionmentioning

confidence: 99%

Critical role of Lin28‐TNFR2 signalling in cardiac stem cell activation and differentiation

Qiu

Yang

et al. 2019

J Cellular Molecular Medi

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“…The important role of STAT3 in cardiac differentiation is also supported by a newly published study. It was discovered that deletion of STAT3 in ESCs would affect the differentiation of ESCs into the mesoderm and cardiac lineage [57]. The mechanisms through which STAT3 regulates CPC generation and cardiac differentiation need to be elucidated in detail in the future work.…”

Section: Discussionmentioning

confidence: 99%

Disruption of histamine/H1R signaling pathway represses cardiac differentiation and maturation of human induced pluripotent stem cells

Zhu

Ding

et al. 2020

Stem Cell Res Ther

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Background:The efficiency and quality of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are crucial for regenerative medicine, disease modeling, drug screening, and the study of the development events during cardiac specification. However, their applications have been hampered by the differentiation efficiency, poor maturation, and high interline variability. Recent studies have reported that histamine plays important roles in hematopoietic stem cell proliferation and neutrophil maturation. However, its roles in cardiovascular tissue regeneration have not been thoroughly investigated. In the current study, we identified a novel physiological function of the histamine/histamine 1 receptor (H 1 R) signal in regulating the differentiation of hiPSC-CMs and heart development.Methods: Transgenic zebrafish model (cmlc2: mCherry) was treated with histamine and histamine receptor (HR) antagonists. Histological morphology and ultrastructure of zebrafish heart were measured. Histamine-deficient pregnant mice (HDC −/− ) were treated with H 1 R antagonist (pyrilamine) by intragastric administration from E8.5 to E18.5. Cardiac histological morphology and ultrastructure were analyzed in neonatal mice, and cardiac function in adult mice was measured. In vitro, histamine and HR antagonists were administrated in the culture medium during hiPSC-CM differentiation at different stages. The efficiency and maturation of cardiac differentiation were evaluated. Finally, histamine-treated hiPSC-CMs were transplanted into ischemic myocardium to detect the possible therapeutic effect.Results: Administration of H 1 R antagonist during heart development induced cardiac dysplasia in zebrafish. Furthermore, using histidine decarboxylase (HDC) knockout mice, we examined abnormal swelling of myocardial mitochondria and autophagy formation under the condition of endogenous histamine deficiency. Histamine significantly promoted myocardial differentiation from human induced pluripotent stem cells (hiPSCs) with better structure and function via a H 1 R-dependent signal. The activation of histamine/H 1 R signaling pathway augmented hiPSC-derived cardiomyocyte (hiPSC-CM) differentiation through the ERK1/2-STAT3 signaling pathway. In addition, histamine-pre-treated hiPSC-CMs were transplanted into the ischemic hearts of myocardial injured mice and exhibited better survival and myocardial protection. Conclusions: Thus, these findings indicated that histamine/H 1 R and its downstream signals were not only involved in cardiac differentiation but also provided a better survival environment for stem cell transplanted into ischemic myocardium.

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“…STAT3, a member of signal transducers and activators of transcription (STAT) family of transcription factors, regulates various cellular function, including embryogenesis, inflammation, and immunity [28,29]. Despite its crucial role in the physiological processes, STAT3 also promotes tumor development and progression.…”

Section: Discussionmentioning

confidence: 99%

ZIPK activates the IL‐6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells

Fan

Qiao

et al. 2021

FEBS Open Bio

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Gastric cancer is one of the most common malignant cancers globally. Chemotherapy resistance remains a major obstacle in the treatment of gastric cancer, and the molecular mechanisms underlying drug resistance are still not well understood. We previously reported that Zipper interacting protein kinase (ZIPK), also known as death‐associated protein kinase3, exerts an oncogenic effect on gastric cancer via activation of Akt/NF‐κB signaling and promotion of stemness. Here, we explored the roles of ZIPK in cisplatin resistance. We report that ZIPK enhances cell proliferation and invasion and reduces the antitumor activity of cisplatin in gastric cancer. In addition, our western blot data suggest that ZIPK activated the IL‐6/STAT3 signaling pathway. Furthermore, ZIPK increased the expression of IL‐6 and multidrug‐resistance genes. Using the STAT3 inhibitor stattic to block the IL‐6/STAT3 signaling pathway strongly increased the sensitivity of ZIPK‐expressed cells to cisplatin. In conclusion, ZIPK may play a role in cisplatin resistance through activation of the IL‐6/ STAT3 signaling pathway. Inhibition of STAT3 in gastric cancer overexpressing ZIPK might have potential to improve the efficacy of cisplatin.

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STAT3-Inducible Mouse ESCs: A Model to Study the Role of STAT3 in ESC Maintenance and Lineage Differentiation

Cited by 6 publications

References 90 publications

Critical role of Lin28‐TNFR2 signalling in cardiac stem cell activation and differentiation

Critical role of Lin28‐TNFR2 signalling in cardiac stem cell activation and differentiation

Disruption of histamine/H1R signaling pathway represses cardiac differentiation and maturation of human induced pluripotent stem cells

ZIPK activates the IL‐6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells

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