By Nina Bai
It took researchers a century to find the genetic glitch that causes orange coloration in cats.
Category: genetics – Page 51
Heterochronic myeloid cell replacement reveals the local brain environment as key driver of microglia aging
Aging, the key risk factor for cognitive decline, impacts the brain in a region-specific manner, with microglia among the most affected cell types. However, it remains unclear whether this is intrinsically mediated or driven by age-related changes in neighboring cells. Here, we describe a scalable, genetically modifiable system for in vivo heterochronic myeloid cell replacement. We find reconstituted myeloid cells adopt region-specific transcriptional, morphological and tiling profiles characteristic of resident microglia. Young donor cells in aged brains rapidly acquired aging phenotypes, particularly in the cerebellum, while old cells in young brains adopted youthful profiles. We identified STAT1-mediated signaling as one axis controlling microglia aging, as STAT1-loss prevented aging trajectories in reconstituted cells. Spatial transcriptomics combined with cell ablation models identified rare natural killer cells as necessary drivers of interferon signaling in aged microglia. These findings establish the local environment, rather than cell-autonomous programming, as a primary driver of microglia aging phenotypes.
Claire Gizowski, Galina Popova, Heather Shin, Wendy Craft, Wenjun Kong, Bernd J Wranik, Yuheng C Fu, Tzuhua D Lin, Baby Martin-McNulty, Po-Han Tai, Kayla Leung, Nicole Fong, Devyani Jogran, Agnieszka Wendorff, David Hendrickson, Astrid Gillich, Andy Chang, Oliver Hahn are current or former employees of Calico Life Sciences LLC. The remaining authors declare no competing interest.
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Researchers uncover critical genetic drivers of the gut’s ‘nervous system’ development
Vanderbilt researchers, including those from the Vanderbilt Brain Institute, have made significant strides in understanding how the enteric nervous system—sometimes called the “brain” of the gut—forms and functions.
In a study published in Cellular and Molecular Gastroenterology and Hepatology, the lab of principal investigator, Michelle Southard-Smith, sheds light on how the SOX10 protein contributes to the development of gut cells that play a role in gastrointestinal motility, or how food moves through the digestive system.
The paper is titled “Single Cell Profiling in the Sox10Dom Hirschsprung Mouse Implicates Hox genes in Enteric Neuron Trajectory Allocation.”
New insights into the epigenetic processes via which neuroinflammation causes memory loss
Neuroinflammation, a prolonged activation of the brain’s immune system prompted by infections or other factors, has been linked to the disruption of normal mental functions. Past studies, for instance, have found that neuroinflammation plays a central role in neurodegenerative diseases, medical conditions characterized by the progressive degradation of cells in the spinal cord and brain.
When inflammation is taking place, cells release proteins that act as signals between immune cells, also known as cytokines. While some studies have linked a specific cytokine called interleukin-1 (IL-1) to changes in brain function, the mechanisms through which it could contribute to a decline in mental capabilities remain poorly understood.
Researchers at the University of Toulouse INSERM and CNRS recently carried out a study involving mice aimed at better understanding these mechanisms. Their paper, published in Nature Neuroscience, particularly focused on neuroinflammation elicited by the parasite Toxoplasma gondii (T. gondii), which is responsible for a well-known illness called toxoplasmosis.
How an autism-linked mutation reduces vasopressin and alters social behavior
A team of researchers has identified for the first time the mechanism linking a mutation in the Shank3 gene with alterations in social behavior. Using a mouse model carrying this autism-associated mutation, the study shows that vasopressin, a brain hormone essential for social relationships, is not properly released in the lateral septum.
The team is from the Cognition and Social Interactions laboratory, led by Félix Leroy at the Institute for Neurosciences, a joint center of the Spanish National Research Council (CSIC) and the Miguel Hernández University (UMH) of Elche.
The work, published in Nature Communications, demonstrates that the proper release of vasopressin in this region regulates social behaviors through two distinct receptor pathways: one controlling sociability and the other controlling social aggression, and that selective activation of these receptors can reverse deficits in social interaction without triggering unwanted aggressive responses.
Apertura Gene Therapy and Rett Syndrome Research Trust Collaborate to Pioneer Advanced Genetic Medicines for Rett Syndrome Using TfR1-Targeted AAV Capsid
NEW YORK and TRUMBULL, Conn., April 30, 2025 /PRNewswire/ — Apertura Gene Therapy, a biotechnology company focused on innovative gene therapy solutions, and the Rett Syndrome Research Trust (RSRT), an organization working to cure Rett Syndrome, today announced a collaboration to license Apertura’s human transferrin receptor 1 capsid (TfR1 CapX). This partnership aims to advance innovative genetic medicine approaches for the treatment of Rett Syndrome, a rare genetic neurological disorder caused by random mutations in the MECP2 gene on the X chromosome that primarily affect females, causing developmental regression and severe motor and language impairments.
Apertura’s TfR1 CapX is an intravenously delivered adeno-associated virus (AAV) capsid engineered to bind the transferrin receptor 1(TfR1), enabling efficient delivery of genetic medicines across the blood-brain barrier (BBB). TfR1 is a well-characterized BBB-crossing receptor, broadly and consistently expressed throughout life—even in the context of neurological disease—making it an attractive target for CNS delivery in disorders like Rett syndrome. Developed by Apertura’s academic founder, Dr. Ben Deverman, Director of Vector Engineering at the Broad Institute, TfR1 CapX has shown strong CNS selectivity in preclinical studies, achieving over 50% neuronal and 90% astrocyte transduction across multiple brain regions. Because Rett syndrome affects the brain diffusely, broader cellular transduction may correlate with greater symptomatic improvement.
Memory consolidation requires reactivation of only three neurons during sleep, research reveals
Researchers at Tsukuba University in Japan report that memories acquired while awake are stored in a more permanent form (called memory consolidation) during the REM stage of sleep, and that this process requires the reactivation of only a few specialized neurons involved in memory formation. They found that three of these neurons are crucial for memory consolidation during REM sleep.
The researchers focused on adult-born neurons (ABNs) in the hippocampal region of the temporal lobe, which are rare neurons known to be essential for maintaining proper memory function as the loss of these cells is observed in Alzheimer’s disease. However, it has remained unclear why the loss of this small neuronal population has such devastating effects on memory.
In the Nature Communications study, specially genetically modified mice, in which the activity of ABNs could be monitored, were exposed to a fear experience, and the researchers examined if the activities of these ABNs during initial memory formation were reproduced during REM sleep, when dreaming is believed to occur.
New AI model predicts which genetic mutations truly drive disease
Scientists at Mount Sinai have created an artificial intelligence system that can predict how likely rare genetic mutations are to actually cause disease. By combining machine learning with millions of electronic health records and routine lab tests like cholesterol or kidney function, the system produces “ML penetrance” scores that place genetic risk on a spectrum rather than a simple yes/no. Some variants once thought dangerous showed little real-world impact, while others previously labeled uncertain revealed strong disease links.