A potential fate decision landscape of the TWEAK/Fn14 axis on stem and progenitor cells: a systematic review

Wang, Sijia; Li, Liang; Cook, Christopher; Zhang, Yufei; Xia, Yumin; Liu, Yale

doi:10.1186/s13287-022-02930-z

Cited by 3 publications

(2 citation statements)

References 75 publications

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“…Aberrant intercellular communications between epithelial, stromal, perivascular cells, endothelial, and immune cells were altered in adenomyosis lesions. Specific enrichment of PTN and TWEAK pathways occurred, both implicated in proliferation, migration, differentiation, and angiogenesis ( Shi et al, 2017 ; Wang et al, 2022 ). Crucial differences in WNT, IGF, and TNF signaling arose between lesions and eutopic endometrium.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics

Chen,

Xu,

et al. 2024

Protein &Amp; Cell

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Adenomyosis is a poorly understood gynecological disorder lacking effective treatments. Controversy persists regarding “invagination” and “metaplasia” theories. The endometrial-myometrial junction (EMJ) connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis, but its in-depth study is just beginning. Using single-cell RNA sequencing and spatial profiling, we mapped transcriptional alterations across eutopic endometrium, lesions, and EMJ. Within lesions, we identified unique epithelial (LGR5+) and invasive stromal (PKIB+) subpopulations, along with WFDC1+ progenitor cells, supporting a complex interplay between “invagination” and “metaplasia” theories of pathogenesis. Further, we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving VEGF and ANGPT pathways. Cell-cell communication differed markedly between ectopic and eutopic endometrium, with aberrant signaling in lesions involving PTN, TWEAK, and WNT cascades. This study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified, dysfunctional signaling, and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics

Chen,

Xu,

et al. 2024

Protein &Amp; Cell

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“…Proinflammatory cytokines, furthermore, can further enhance TNFR2 expression (Winzen et al, 1993;Wang et al, 2006;Al-Lamki et al, 2008;Hurrell et al, 2019;Medler and Wajant, 2019;Suto et al, 2022). During development Fn14 is strongly and temporally expressed but later, in the fully developed organism, Fn14 expression is restricted to various types of pluripotent and unipotent stem cells (Wang et al, 2022). Worth mentioning is, however, that a plethora of growth factors, cytokines, pathogenassociated molecular patterns (PAMPs) and physical stressors induce high Fn14 expression in non-hematological cells resulting in a tissue injury-associated expression pattern (Winkles, 2008;Burkly et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Fn14 and TNFR2 as regulators of cytotoxic TNFR1 signaling

Siegmund,

Zaitseva,

Wajant

2023

Front. Cell Dev. Biol.

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Tumor necrosis factor (TNF) receptor 1 (TNFR1), TNFR2 and fibroblast growth factor-inducible 14 (Fn14) belong to the TNF receptor superfamily (TNFRSF). From a structural point of view, TNFR1 is a prototypic death domain (DD)-containing receptor. In contrast to other prominent death receptors, such as CD95/Fas and the two TRAIL death receptors DR4 and DR5, however, liganded TNFR1 does not instruct the formation of a plasma membrane-associated death inducing signaling complex converting procaspase-8 into highly active mature heterotetrameric caspase-8 molecules. Instead, liganded TNFR1 recruits the DD-containing cytoplasmic signaling proteins TRADD and RIPK1 and empowers these proteins to trigger cell death signaling by cytosolic complexes after their release from the TNFR1 signaling complex. The activity and quality (apoptosis versus necroptosis) of TNF-induced cell death signaling is controlled by caspase-8, the caspase-8 regulatory FLIP proteins, TRAF2, RIPK1 and the RIPK1-ubiquitinating E3 ligases cIAP1 and cIAP2. TNFR2 and Fn14 efficiently recruit TRAF2 along with the TRAF2 binding partners cIAP1 and cIAP2 and can thereby limit the availability of these molecules for other TRAF2/cIAP1/2-utilizing proteins including TNFR1. Accordingly, at the cellular level engagement of TNFR2 or Fn14 inhibits TNFR1-induced RIPK1-mediated effects reaching from activation of the classical NFκB pathway to induction of apoptosis and necroptosis. In this review, we summarize the effects of TNFR2- and Fn14-mediated depletion of TRAF2 and the cIAP1/2 on TNFR1 signaling at the molecular level and discuss the consequences this has in vivo.

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Identification of programmed cell death-related genes and diagnostic biomarkers in endometriosis using a machine learning and Mendelian randomization approach

Xie,

He,

Feng

et al. 2024

Front. Endocrinol.

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BackgroundEndometriosis (EM) is a prevalent gynecological disorder frequently associated with irregular menstruation and infertility. Programmed cell death (PCD) is pivotal in the pathophysiological mechanisms underlying EM. Despite this, the precise pathogenesis of EM remains poorly understood, leading to diagnostic delays. Consequently, identifying biomarkers associated with PCD is critical for advancing the diagnosis and treatment of EM.MethodsThis study used datasets from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) following preprocessing. By cross-referencing these DEGs with genes associated with PCD, differentially expressed PCD-related genes (DPGs) were identified. Enrichment analyses for KEGG and GO pathways were conducted on these DPGs. Additionally, Mendelian randomization and machine learning techniques were applied to identify biomarkers strongly associated with EM.ResultsThe study identified three pivotal biomarkers: TNFSF12, AP3M1, and PDK2, and established a diagnostic model for EM based on these genes. The results revealed a marked upregulation of TNFSF12 and PDK2 in EM samples, coupled with a significant downregulation of AP3M1. Single-cell analysis further underscored the potential of TNFSF12, AP3M1, and PDK2 as biomarkers for EM. Additionally, molecular docking studies demonstrated that these genes exhibit significant binding affinities with drugs currently utilized in clinical practice.ConclusionThis study systematically elucidated the molecular characteristics of PCD in EM and identified TNFSF12, AP3M1, and PDK2 as key biomarkers. These findings provide new directions for the early diagnosis and personalized treatment of EM.

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A potential fate decision landscape of the TWEAK/Fn14 axis on stem and progenitor cells: a systematic review

Cited by 3 publications

References 75 publications

Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics

Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics

Fn14 and TNFR2 as regulators of cytotoxic TNFR1 signaling

Identification of programmed cell death-related genes and diagnostic biomarkers in endometriosis using a machine learning and Mendelian randomization approach

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