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http://dx.doi.org/10.15252/embj.201797813 | DOI Listing |
Stem Cell Rev Rep
September 2025
Stem Cells and Metabolism Research Program (STEMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.
Mutations in Delta Like Non-Canonical Notch Ligand 1 (DLK1), a paternally expressed imprinted gene, underlie central precocious puberty (CPP), yet the mechanism remains unclear. To test the hypothesis that DLK1 plays a role in gonadotropin releasing hormone (GnRH) neuron ontogeny, 75 base pairs were deleted in both alleles of DLK1 exon 3 with CRISPR-Cas9 in human pluripotent stem cells (hPSCs). This line, exhibiting More than 80% loss of DLK1 protein, was differentiated into GnRH neurons by dual SMAD inhibition (dSMADi), FGF8 treatment and Notch inhibition, as previously described, however, it did not exhibit accelerated GNRH1 expression.
View Article and Find Full Text PDFElife
September 2025
Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, United States.
Wnt proteins are critical signaling molecules in developmental processes across animals. Despite intense study, their evolutionary roots have remained enigmatic. Using sensitive sequence analysis and structure modeling, we establish that the Wnts are part of a vast assemblage of domains, the Lipocone superfamily, defined here for the first time.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
September 2025
Univ. of Pennsylvania, Medicine, Philadelphia, Pennsylvania, United States.
Lymphangioleiomyomatosis (LAM) is a rare lung disease caused by hyperactivation of the mechanistic/mammalian target of rapamycin 1 (mTORC1) growth pathway in a subset of mesenchymal lung cells. Histopathologically, LAM lesions have been described as immature smooth muscle-like cells positive for the immature melanocytic marker HMB45/PMEL/gp100 and phosphorylated ribosomal protein S6 (pS6). Advances in single cell sequencing (scRNA-seq) technology allowed us to group LAM cells according to their expression of cancer stem cell (CSC) genes and identify three clusters: a high CSC-like state (SLS), an intermediate state, and a low CSC-like inflammatory state (IS).
View Article and Find Full Text PDFPLoS One
September 2025
Department of Zoology, Baba Guru Nanak University, Nankana Sahib, Pakistan.
Secreted frizzled-related protein 4 (sFRP4) plays a fundamental role in the regulation of Wnt signalling, which is crucial for cellular proliferation and differentiation. The sFRP4 has garnered significant interest as a therapeutic target for metabolic diseases and cancer due to its mechanism of action. Although existing sFRP4 modulators show limited specificity and notable off-target effects, our study explores the potential of known bioactive compounds as more selective and less toxic alternatives.
View Article and Find Full Text PDFCisplatin resistance significantly limits the efficacy of chemotherapy in non-small cell lung cancer, necessitating the development of new strategies to overcome this barrier. This in vitro study aimed to elucidate the mechanism by which β-Ele reverses cisplatin resistance in lung adenocarcinoma cells via the LINC00511-mediated glycolysis and Wnt/β-catenin signaling pathways. The cisplatin-resistant human lung adenocarcinoma cell line (A549/DDP), with either LINC00511 overexpression or knockdown, was established through plasmid transfection.
View Article and Find Full Text PDF