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The cytoskeleton plays a crucial role in regulating cellular behavior, acting as both a structural framework and a mediator of mechanical and biochemical signals that influence cell fate. In the context of cellular reprogramming, modifications to the cytoskeleton can have profound effects on lineage commitment and differentiation efficiency. This review explores the impact of mechanical forces such as substrate stiffness, topography, extracellular fluid viscosity, and cell seeding density on cytoskeletal organization and mechanotransduction pathways, including Rho/ROCK and YAP/TAZ signaling. Additionally, we examine the influence of biochemical agents that modulate cytoskeletal dynamics, such as actin and microtubule polymerization inhibitors, and their effects on stem cell differentiation. By understanding how cytoskeletal remodeling governs cellular identity, this review highlights potential strategies for improving reprogramming efficiency and directing cell fate by manipulating mechanical and biochemical cues.
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http://dx.doi.org/10.3389/fmolb.2025.1538806 | DOI Listing |
Sci Adv
September 2025
Department of Cell & Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Somatic mitochondrial DNA (mtDNA) mutations are frequently observed in tumors, yet their role in pediatric cancers remains poorly understood. The heteroplasmic nature of mtDNA-where mutant and wild-type mtDNA coexist-complicates efforts to define its contribution to disease progression. In this study, bulk whole-genome sequencing of 637 matched tumor-normal samples from the Pediatric Cancer Genome Project revealed an enrichment of functionally impactful mtDNA variants in specific pediatric leukemia subtypes.
View Article and Find Full Text PDFSci Transl Med
September 2025
Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
Hepatocyte apoptosis is a key feature of metabolic dysfunction-associated steatohepatitis (MASH), but the fate of apoptotic hepatocytes in MASH is poorly understood. Here, we explore the hypotheses that clearance of dead hepatocytes by liver macrophages (efferocytosis) is impaired in MASH because of low expression of the efferocytosis receptor T cell immunoglobulin and mucin domain containing 4 (TIM4; gene ) by MASH liver macrophages, which then drives liver fibrosis in MASH. We show that apoptotic hepatocytes accumulate in human and experimental MASH, using mice fed the fructose-palmitate-cholesterol (FPC) diet or the high-fat, choline-deficient amino acid-defined (HF-CDAA) diet.
View Article and Find Full Text PDFFunct Integr Genomics
September 2025
Department of Plastic Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Keloid scarring and Metabolic Syndrome (MS) are distinct conditions marked by chronic inflammation and tissue dysregulation, suggesting shared pathogenic mechanisms. Identifying common regulatory genes could unveil novel therapeutic targets. Methods.
View Article and Find Full Text PDFActa Neuropathol Commun
September 2025
Department of Stem Cell and Regenerative Biotechnology, School of Advanced Biotechnology, Molecular & Cellular Reprogramming Center, Institute of Advanced Regenerative Science, and Institute of Health, Aging & Society, Konkuk University, Seoul, 05029, Republic of Korea.
Proc Natl Acad Sci U S A
September 2025
Department of Biochemical Pathophysiology, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Adrenal lipomas are benign tumors containing ectopic adipose tissue in the adrenal gland, an organ that normally lacks both adipocytes and their progenitors. The origin of this ectopic fat remains enigmatic, and the absence of a genetic animal model has hindered its investigation. Phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P], a key signaling lipid that regulates cellular growth and differentiation, is tightly regulated by the lipid phosphatases PTEN (phosphatase and tensin homolog) and SHIP2 (SH2-containing inositol phosphatase 2).
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