Linking epigenetics and metabolism in neurogenesis!
Epigenetic regulation and metabolism are tightly coordinated during progenitor cell growth but the processes linking this crosstalk is not well understood.
The researchers examined in neural stem cells the role of PHF8, a histone demethylase whose mutations are linked to Siderius-Hamel syndrome, a rare neurodevelopmental disorder.
The authors show that PHF8 regulates neural progenitor proliferation by coordinating epigenetic and metabolic programs and drives serine biosynthesis by maintaining chromatin accessibility of serine synthesis genes.
They also demonstrate that loss of PHF8 disrupts metabolism, autophagy, and vesicle formation and its deficiency leads to DNA damage and halts neurogenesis in vivo. sciencenewshighlights ScienceMission https://sciencemission.com/Epigenetic-regulation-of-serine-biosynthesis
Progenitor proliferation during neurodevelopment requires tight coordination of epigenetic regulation and metabolism. However, the crosstalk between these processes remains poorly understood. To investigate this, we examine in neural stem cells the role of PHF8, a histone demethylase whose mutations are linked to Siderius-Hamel syndrome, a rare neurodevelopmental disorder. Through an integrated multi-omics approach — combining transcriptomics, epigenomics, and metabolomics — we identify PHF8 as a key driver of the serine biosynthesis pathway, safeguarding the intracellular serine pool essential for neural progenitor proliferation. PHF8 fine-tunes chromatin accessibility at promoters of metabolic genes, ensuring their activation during development. Loss of PHF8 disrupts amino acid metabolism, blocks autophagy, and hinders vesicle formation.
Schwann cell-derived exosomes are powerful promoters of nerve repair, capable of enhancing axon regrowth, remyelination, and functional recovery in numerous models. These effects are mediated via multifactorial cargo (miRNAs, mRNAs, proteins) that modulate neurons, glia, endothelial, and immune cells. Importantly, what began as a novel biological insight is now rapidly moving toward therapeutic innovation. Schwann cell-derived exosomes thus represent both a novel mode of glia–neuron communication and a promising avenue for next-generation therapies for nerve regeneration.
Summary: Establishing Qualia Structure Paradigm
Do subjective conscious experience and objective brain matters belong to completely different worlds? How are qualia, the contents of consciousness, related to the brain? The question of consciousness and the brain is not only of scientific interest, but it is also directly related to the problems associated with difficulties in understanding human feelings in the real world. Because qualia are difficult to even define in objective terms, conventional studies of consciousness have attempted to explore their neural correlates by fixing perceptual stimuli and reducing experience to binary judgments, such as seen vs. not seen. Recently, we have established a new paradigm to characterize the structure of qualia by measuring the similarity between visual qualia on a large scale, and to reveal their neural correlates and their information structure.
Over the past decades, neuroscience studies have painted an increasingly detailed picture of the human brain, its organization and how it supports various functions. To plan and execute desired behaviors in changing circumstances, networks of neurons in the brain can either work together or suppress each other, thus employing both cooperative and competitive interaction strategies.
Researchers at University of Oxford, University of Cambridge, McGill University, University of Aarhus and Pompeu Fabra University recently set out to better understand the mammalian brain’s underlying dynamics, specifically how its underlying architecture balances cooperative and competitive interactions between neural circuits. Their paper, published in Nature Neuroscience, offers new insight that could both improve the understanding of the brain and inform the development of brain-inspired computational models.
“Building models of the brain is an important part of modern neuroscience,” Andrea Luppi, first author of the paper, told Medical Xpress. “As Nobel winner Reichard Feynman said, ‘what I cannot create, I do not understand.’ Most current models, however, share a limitation. Everyday experience, from focusing attention or switching between tasks, also reveals that brain systems must compete for limited resources.
A new study from the University of Geneva points to the brain’s waste-clearance system — the glymphatic system — as a possible piece of the psychosis puzzle. In people with 22q11.2 deletion syndrome, a high-risk genetic condition, researchers found developmental differences in an MRI-derived marker linked to glymphatic function, along with associations to hippocampal excitation/inhibition balance and psychosis vulnerability.
A team from UNIGE shows that early alterations in the brain’s clearance system could contribute to vulnerability to psychosis.
How can we explain the onset of psychotic symptoms characteristic of schizophrenia? Despite their major and often irreversible impact on intellectual abilities and autonomy, the biological mechanisms that precede their emergence remain poorly understood. A team from the Department of Psychiatry at the Faculty of Medicine and the Synapsy Center for Neuroscience Research in Mental Health at the University of Geneva (UNIGE) provides new insight into this question. Early dysfunction of the glymphatic system, the network responsible for removing waste from the brain, could be a key vulnerability factor. This research has been published in Biological Psychiatry: Global Open Science.
Hallucinations and delusions are among the characteristic psychotic symptoms of schizophrenia spectrum disorders, which may also be accompanied by social withdrawal and cognitive decline. These disorders, considered neurodevelopmental conditions, most often emerge during adolescence or early adulthood and have an estimated prevalence of 0.5–3% in the general population.
Liu et al. present via https://bit.ly/4bV6X0s (Original research, Hepatology section).
A major step forward for translational research, this study shows that human organoid systems can support replication of multiple hepatitis E virus genotypes—offering a powerful new platform for studying infection and testing therapies.
Background Hepatitis E virus (HEV), the leading global cause of acute viral hepatitis, lacks robust in vitro models for virology and pathogenesis research.
Objective We evaluated induced pluripotent stem cell (iPSC)-induced human liver, intestinal and brain organoids (hLOs, hIOs and hBOs) as platforms for HEV infection and replication.
Methods Multilineage organoids were infected with clinical HEV genotypes 1, 3 and 4. Viral tropism, host responses and antiviral efficacy were assessed.
Results All organoids supported the complete life cycle of HEV. hLOs exhibited infection in hepatocytes, cholangiocytes, macrophages and stellate cells, accompanied by elevated interleukin-6 levels, impaired hepatic function (reduced secretion of albumin and Factor IX) and increased levels of alanine aminotransferase and aspartate aminotransferase, indicating hepatocellular injury.