Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: Argininosuccinate synthase (ASS1) is a pivotal enzyme involved in the urea cycle, playing a crucial role in aspartate catabolism, arginine and nitric oxide biosynthesis. These biological processes are crucial for the growth and development of mammals. However, the functions of urea cycle-related genes in mouse embryonic stem cells (mESCs) remain largely unclear. Here, we investigated the impact of ASS1 knockout on the mESCs pluripotency and its role in determining cell fate.
Methods: ASS1 was knocked out in mESCs using CRISPR-Cas9. Changes in pluripotency post-knockout were analyzed via immunofluorescence, Western blotting, differentiation assays, and chimera formation. Cardiomyocyte differentiation assays evaluated the impact on cardiac lineage specification. RNA sequencing (RNA-seq), Western blotting, and signaling pathway inhibitors were used to investigate alterations in molecular signatures and regulatory mechanisms.
Results: ASS1 knockout did not compromise mESCs pluripotency maintenance or self-renewal but perturbed the cell cycle. It upregulated mesendoderm markers while downregulating ectoderm markers. Notably, ASS1 deficiency enhanced cardiomyocyte differentiation potential. The multi-lineage differentiation markers were reversed by either ASS1 overexpression or treatment with Wnt/β-catenin inhibitors.
Conclusions: ASS1 knockout directs mESCs toward mesendoderm lineage commitment, thereby promoting beating cardiomyocyte generation. Thus, ASS1 acts as a regulatory switch whose absence drives mesendoderm differentiation and enhances cardiomyocyte production.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403944 | PMC |
| http://dx.doi.org/10.1186/s13287-025-04622-w | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The role of ASS1 in mouse embryonic stem cell differentiation into mesendoderm lineages.
Stem Cell Res Ther
September 2025
Research Center for Animal Genetic Resources of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot, 010020, China.
Background: Argininosuccinate synthase (ASS1) is a pivotal enzyme involved in the urea cycle, playing a crucial role in aspartate catabolism, arginine and nitric oxide biosynthesis. These biological processes are crucial for the growth and development of mammals. However, the functions of urea cycle-related genes in mouse embryonic stem cells (mESCs) remain largely unclear.
View Article and Find Full Text PDFBeyond the Limit: MYC Mediates Tumor Immune Escape.
Pharmaceuticals (Basel)
June 2025
Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
MYC is an aberrantly regulated transcription factor implicated in approximately 70% of human tumors, where it extensively modulates signaling pathways associated with cancer progression. Inactivating MYC has been shown to inhibit tumor growth and even induce sustained tumor regression across various cancer types, a phenomenon referred to as oncogene addiction. However, in vitro studies reveal that the knockout or knockdown of MYC in numerous tumor cell lines does not necessarily result in cell death, despite these tumors exhibiting MYC addiction in vivo.
View Article and Find Full Text PDFThe novel synbiotic (Lactiplantibacillus plantarum and galacto-oligosaccharides) ameliorates obesity-related metabolic dysfunction: Arginine as a key mediator signaling molecule.
J Adv Res
June 2025
College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China. Electronic address:
Objective: This study aimed to develop a novel synbiotic composed of Lactiplantibacillus plantarum LLY-606 and galacto-oligosaccharides (GOS) to improve lipid metabolism in obesity.
Design: Through genome-wide analysis using COG and CAZy databases, we identified GOS as a specific growth substrate for Lactiplantibacillus plantarum LLY-606. The efficacy of this synbiotic (LP-GOS) was evaluated in both obese individuals and high-fat diet-induced obese mice.
Metabolic remodelling produces fumarate via the aspartate-argininosuccinate shunt in macrophages as an antiviral defence.
Nat Microbiol
May 2025
State Key Laboratory of Molecular Oncology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
Metabolic remodelling underpins macrophage effector functions in response to various stimuli, but the mechanisms involved are unclear. Here we report that viral-infection-induced inflammatory stimulation causes a rewiring of the urea cycle and the tricarboxylic acid cycle metabolism in macrophages to form a cyclic pathway called the aspartate-argininosuccinate (AAS) shunt. Using RNA sequencing, unbiased metabolomics and stable isotope tracing, we found that fumarate generated from the AAS shunt is driven by argininosuccinate synthase (ASS1) in the cytosol and potentiates inflammatory effects.
View Article and Find Full Text PDFFoxO transcription factors regulate urea cycle through Ass1.
Biochem Biophys Res Commun
December 2024
Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan; Nutrigenomics Research Group, Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan; Department of Internal Medicine (Endocrinology and Metabolism), Institute of Med
Article Synopsis
- A high-protein diet leads the liver to increase enzymes for amino acid breakdown, particularly enhancing the urea cycle for nitrogen excretion.
- KLF15 is crucial for amino acid metabolism, and recent research shows that FoxO transcription factors are significant regulators of KLF15 in the liver.
- The study found that FoxOs directly affect urea cycle-related amino acids and regulate hepatic Ass1 expression independently of KLF15, particularly under high-protein conditions.