TGFβ Family Signaling Pathways in Pluripotent and Teratocarcinoma Stem Cells’ Fate Decisions: Balancing Between Self-Renewal, Differentiation, and Cancer

Abstract

The transforming growth factor-β (TGFβ) family factors induce pleiotropic effects and are involved in the regulation of most normal and pathological cellular processes. The activity of different branches of the TGFβ family signaling pathways and their interplay with other signaling pathways govern the fine regulation of the self-renewal, differentiation onset and specialization of pluripotent stem cells in various cell derivatives. TGFβ family signaling pathways play a pivotal role in balancing basic cellular processes in pluripotent stem cells and their derivatives, although disturbances in their genome integrity induce the rearrangements of signaling pathways and lead to functional impairments and malignant transformation into cancer stem cells. Therefore, the identification of critical nodes and targets in the regulatory cascades of TGFβ family factors and other signaling pathways, and analysis of the rearrangements of the signal regulatory network during stem cell state transitions and interconversions, are key issues for understanding the fundamental mechanisms of both stem cell biology and cancer initiation and progression, as well as for clinical applications. This review summarizes recent advances in our understanding of TGFβ family functions in naїve and primed pluripotent stem cells and discusses how these pathways are involved in perturbations in the signaling network of malignant teratocarcinoma stem cells with impaired differentiation potential.

Synergistic effect of Huyang Yangkun Formula and embryonic stem cells on 4-vinylcyclohexene diepoxide induced premature ovarian insufficiency in mice

“…Also the formula in our previous study was shown to promote ovarian follicle developing in 4-vinylcyclonhexene diepoxide (VCD)-induced POI rats, and the gene expression of transforming growth factor beta-activated kinase 1 (TAK1) was significantly different between the the control, VCD and VCD + HYYKF groups [ 18 ]. TAK1 is an important signaling molecule in the transforming growth factor beta (TGF-β) signaling pathway, and the TGF-β signaling pathway has a wide range of regulating functions by interacting with other pathways and plays a critical role in the physiological and pathological processes of pluripotent stem cells [ 19 ]. We hypothesized that HYYKF could enhance the treatment effect of ESCs on POI by regulating the TGF-β/TAK1 pathway.…”

Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells

“…In contrast to the zygote and early two-cells, from the comparisons between the mid-late two-cells and TBLCs, TBLCs showed high expression levels of pluripotency genes and low expression of totipotency genes. In the predicted pathway regulation analyses, many of the differentiation-related genes are enriched in the TBLCs, including Tgf1 and Fgf2 [16,19].…”

SVF-derived extracellular vesicles carry characteristic miRNAs in lipedema

“…When identifying potential target genes of the significantly up-and down-regulated miRNAs, we found regulatory molecules in Wnt signaling pathway, which play an important role in regulation of inflammation, oxidative stress and senescence 64 . Interestingly, our distinct secreted miRNAs were predicted to regulate a dynamic crosstalk of Wnt and another prominent pathway, NOTCH via targeting SMADs, which are also well-know nmediators of inflammatory, fibrotic, oxidative, proliferative, metabolic and angiogenic events [65][66][67] . The NOTCH super-signaling pathway plays an emerging role controlling key steps in the immune system and tissue homeostasis during repair and regeneration 68 .…”