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Differentiated cells can be converted into pluripotent stem cells by expressing the transcription factors OCT4, SOX2, KLF4, and MYC (OSKM) in a process known as reprogramming. Here, using single-cell RNA sequencing of pancreas undergoing reprogramming, we identify markers along the trajectory from acinar cell identity to pluripotency. These markers allow direct in situ visualization of cells undergoing dedifferentiation and acquiring features of early and advanced intermediate reprogramming. We also find that a fraction of cells do not dedifferentiate upon OSKM expression and are characterized by stress markers of the REG3 and AP-1 families. Importantly, most markers of intermediate reprogramming in the pancreas are also observed in stomach, colon, and cultured fibroblasts expressing OSKM. Among them is LY6A, a protein characteristic of progenitor cells and generally upregulated during tissue repair. Our roadmap defines intermediate reprogramming states that could be functionally relevant for tissue regeneration and rejuvenation.
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http://dx.doi.org/10.1016/j.stemcr.2022.09.009 | DOI Listing |
Cell Rep
September 2025
Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address:
Adenylosuccinate lyase deficiency (ADSLd) is a rare autosomal recessive purine metabolism disorder with several clinical manifestations. While toxic substrate accumulation is a known hallmark, no additional molecular mechanisms have been established. Here, we show that ADSLd is associated with mitochondrial dysfunction, including increased fragmentation, impaired respiration, and reduced ATP production.
View Article and Find Full Text PDFJ Biol Chem
September 2025
Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400094, India. Electronic address:
Breast cancer, a leading cause of mortality, exhibits significant heterogeneity across molecular subtypes, with tumor hypoxia contributing to poor therapeutic outcomes. The present study investigates the role of ZMYND8, a hypoxia-responsive epigenetic factor, in regulating carbohydrate metabolism in concert with HIF1α in breast cancer. In adherent cells as well as in 3D MCTS, ZMYND8 expression is elevated under hypoxic conditions.
View Article and Find Full Text PDFCurr Cancer Drug Targets
August 2025
Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, 13210, New York.
Angew Chem Int Ed Engl
September 2025
Department of Chemical and Biological Engineering, University of Colorado, Boulder, 3415 Colorado Avenue, Boulder, CO, 80303, USA.
Assembly-line enzymes carry out multistep synthesis of important metabolites by using acyl carrier proteins (ACPs) to shuttle intermediates along defined sequences of active sites. Despite longstanding interest in reprogramming these systems for metabolic engineering and biosynthetic chemistry, the mechanisms underlying their reaction order remain poorly understood and difficult to control. Here we describe a β-ketoacyl-ACP reductase from Pseudomonas putida (PpFabG4) with an unusual selectivity for medium chains and use it to explore the molecular basis of substrate specificity in enzymes that pull intermediates from fatty acid synthesis, a common route to specialized products.
View Article and Find Full Text PDFJ Biomed Sci
September 2025
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan.
Aging is the foremost risk factor for metabolic syndrome and atherosclerosis, which is a principal cause of cardiovascular diseases (CVDs). Vascular endothelial cells (ECs), which line the vascular intima, play a central role in maintaining vascular homeostasis. Their dysfunction, marked by impaired barrier function, inflammation, and metabolic dysregulation, constitutes an early and pivotal event in atherogenesis.
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