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IGF2BPs, a subclass of RNA-binding proteins, regulate cellular differentiation, proliferation and migration during multiple organs development, but their functions in liver development still remain unclear. Here, in this study, whole-mount in situ hybridization showed that igf2bp1 was constantly and stably expressed at early stages of embryo development in zebrafish. Both the morpholino-induced knockdown and CRISPR/Cas9-mediated knockout of igf2bp1 led to a reduced-size liver phenotype. Further analysis revealed that igf2bp1 is required for hepatic outgrowth, but not for hepatoblast specification and budding. Deficiency of igf2bp1 resulted in reduced cell proliferation, but had no effect on apoptosis. Therefore, we concluded that igf2bp1 is a critical factor to regulate hepatic outgrowth via cell proliferation during early liver development in zebrafish.
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http://dx.doi.org/10.1016/j.gene.2020.144632 | DOI Listing |
Blood
August 2025
University of Miami School of Medicine, Miami, Florida, United States.
The current approach to minimize transplant-associated complications, including graft-versus-host disease (GVHD) includes long-term pharmacological immune suppression frequently accompanied by unwanted side effects. Advances in targeted immunotherapies regulating alloantigen responses in the recipient continue to reduce the need for pan-immunosuppression. Here, in vivo targeting of the TNF superfamily receptor TNFRSF25 and the high affinity IL-2 receptor with a TL1A-Ig fusion protein and low dose IL-2, respectively was used to pre-treat recipient mice prior to allogeneic-HSCT (aHSCT).
View Article and Find Full Text PDFCancer Discov
July 2025
National Institutes of Health, Bethesda, MD, United States.
Given the propensity of aggressive epithelial tumors to form hepatic metastases, we performed an in vivo cDNA screen using the mouse liver and KRASG12D/TP53R273H pancreatic cells to identify the RNA binding protein GCN1 as integral component of hepatic outgrowth. RNAi experiments reveal that GCN1 triggers the ISR to activate serine, folate, and methionine biosynthetic pathways together with amino acid transporters, which act in concert to facilitate acquisition of metabolites and to restore redox homeostasis. Alongside activation of the ISR, we found that GCN1 also functions in the nucleus where it interacts with HNRNPK to suppress the expression of MHC-I molecules, and natural killer (NK) ligands.
View Article and Find Full Text PDFbioRxiv
May 2025
The Department of Tumor Microenvironment and Metastasis, The Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, USA.
Uveal melanoma (UM) results in fatal liver metastasis, yet little is known about the interactions between UM and host cells in the tumor microenvironment that promote this distinctive proclivity. Here, we used single cell (sc)-RNA-Seq analysis of UM-hepatic stellate cell (HSC) co-cultures to demonstrate that HSCs enriched for UM cell states that expressed genes implicated in cell survival, metabolic reprogramming and angiogenesis. A lead candidate driver of HSC reprogramming was the TGF-β family member GDF15, which was associated with a metastatic UM phenotype.
View Article and Find Full Text PDFPancreas
May 2025
Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, USA.
Objective: Identify how surgical resection of pancreatic ductal adenocarcinoma (PDAC) affects systemic minimal residual disease (MRD).
Methods: Pancreatic tumors were generated by orthotopic implantation of tumor cells into the pancreas of immunocompetent mice. Tumor resection was carried out via distal pancreatectomy and splenectomy.
iScience
May 2025
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
The liver is an important metastatic organ that contains many innate immune cells, yet little is known about their role in anti-metastatic defense. We investigated how invariant natural killer T (iNKT) cells influence colorectal cancer-derived liver metastasis using different models in immunocompetent mice. We found that hepatic iNKT cells promote metastasis by creating a supportive niche for disseminated cancer cells.
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