Publications by authors named "Chloe Delepine"

Human cerebral organoids derived from induced pluripotent stem cells can recapture early developmental processes and reveal changes involving neurodevelopmental disorders. Mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene are associated with Rett syndrome, and disease severity varies depending on the location and type of mutation. Here, we focused on neuronal activity in Rett syndrome patient-derived organoids, analyzing two types of MeCP2 mutations - a missense mutation (R306C) and a truncating mutation (V247X) - using calcium imaging with three-photon microscopy.

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Circular RNAs (circRNAs) are noncoding RNAs abundant in brain tissue, and many are derived from activity-dependent, linear mRNAs encoding for synaptic proteins, suggesting that circRNAs may directly or indirectly play a role in regulating synaptic development, plasticity, and function. However, it is unclear if the circular forms of these RNAs are similarly regulated by activity and what role these circRNAs play in developmental plasticity. Here, we employed transcriptome-wide analysis comparing differential expression of both mRNAs and circRNAs in juvenile mouse primary visual cortex (V1) following monocular deprivation (MD), a model of developmental plasticity.

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This study reveals that Fc-enhanced anti-CTLA-4 harnesses novel mechanisms to overcome the limitations of conventional anti-CTLA-4, effectively treating poorly immunogenic and treatment-refractory cancers. Our findings support the development of a new class of immuno-oncology agents, capable of extending clinical benefit to patients with cancers resistant to current immunotherapies.

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Microsatellite stable metastatic colorectal cancer (MSS mCRC; mismatch repair proficient) has previously responded poorly to immune checkpoint blockade. Botensilimab (BOT) is an Fc-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody designed to expand therapy to cold/poorly immunogenic solid tumors, such as MSS mCRC. BOT with or without balstilimab (BAL; anti-PD-1 antibody) is being evaluated in an ongoing expanded phase 1 study.

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Article Synopsis
  • Extracellular histones released during cell death contribute to inflammation and cell death, especially in sepsis, highlighting their harmful effects.
  • Clusterin (CLU) is an extracellular protein that may counteract the adverse effects of histones by binding to them and neutralizing their harmful properties.
  • In sepsis patients, lower CLU levels correlate with increased mortality, and studies show that CLU supplementation can enhance survival rates in mouse models of sepsis.
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Although motor cortex is crucial for learning precise and reliable movements, whether and how astrocytes contribute to its plasticity and function during motor learning is unknown. Here, we report that astrocyte-specific manipulations in primary motor cortex (M1) during a lever push task alter motor learning and execution, as well as the underlying neuronal population coding. Mice that express decreased levels of the astrocyte glutamate transporter 1 (GLT1) show impaired and variable movement trajectories, whereas mice with increased astrocyte Gq signaling show decreased performance rates, delayed response times, and impaired trajectories.

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Human cerebral organoids are unique in their development of progenitor-rich zones akin to ventricular zones from which neuronal progenitors differentiate and migrate radially. Analyses of cerebral organoids thus far have been performed in sectioned tissue or in superficial layers due to their high scattering properties. Here, we demonstrate label-free three-photon imaging of whole, uncleared intact organoids (~2 mm depth) to assess early events of early human brain development.

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Rett syndrome (RTT) is a devastating neurodevelopmental disorder without effective treatments. Attempts at developing targetted therapies have been relatively unsuccessful, at least in part, because the genotypical and phenotypical variability of the disorder. Therefore, identification of biomarkers of response and patients' stratification are high priorities.

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Article Synopsis
  • Rett syndrome (RTT) is a rare disorder mainly caused by changes in the MECP2 gene, affecting brain development and function in both genders.
  • Research showed that astrocytes (a type of brain cell) lacking MECP2 have issues with microtubule dynamics, which are important for cell function.
  • Treatment with tubastatin A, an HDAC6 inhibitor, helped restore these dynamics and improved exploratory behavior in male mice with RTT, indicating potential for new treatments.
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Cerebral organoids generated from human pluripotent stem cells (hiPSCs) are unique in their ability to recapitulate human-specific neurodevelopmental events. They are capable of modeling the human brain and its cell composition, including human-specific progenitor cell types; ordered laminar compartments; and both cell-specific transcriptional signatures and the broader telencephalic transcriptional landscape. The serine/threonine kinase, GSK3β, plays a critical role in neurodevelopment, controlling processes as varied as neurogenesis, morphological changes, polarization, and migration.

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Organoids are biological systems grown and are observed to self-organize into 3D cellular tissues of specific organs. Brain organoids have emerged as valuable models for the study of human brain development in health and disease. Researchers are now in need of improved culturing and imaging tools to capture the dynamics of development processes in the brain.

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Article Synopsis
  • - Rett syndrome (RTT) is a rare disorder that causes loss of motor and language skills, as well as cognitive impairment, primarily due to mutations in the MECP2 gene.
  • - Research shows that the absence of MECP2 in glial cells negatively affects neurons, but restoring MECP2 in astrocytes in mice improves movement, anxiety, and lifespan.
  • - The study found that the drug Epothilone D can restore microtubule transport in astrocytes lacking MECP2 and improve behavior in RTT-affected mice, suggesting potential for innovative treatment.
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Mutations in the gene encoding the transcriptional modulator methyl-CpG binding protein 2 (MeCP2) are responsible for the neurodevelopmental disorder Rett syndrome which is one of the most frequent sources of intellectual disability in women. Recent studies showed that loss of Mecp2 in astrocytes contributes to Rett-like symptoms and restoration of Mecp2 can rescue some of these defects. The goal of this work is to compare gene expression profiles of wild-type and mutant astrocytes from Mecp2(308/y) mice (B6.

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Rett syndrome (RTT) is a severe neurodevelopmental disease caused by mutations in methyl-CpG-binding protein 2 (MECP2), which encodes a transcriptional modulator of many genes including BDNF. BDNF comprises nine distinct promoter regions, each triggering the expression of a specific transcript. The role of this diversity of transcripts remains unknown.

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Mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene have been described in girls with Rett-like features and early-onset epileptic encephalopathy including infantile spasms. Milder phenotypes have been associated with sequence variations in the 3'-end of the CDKL5 gene. Identification of novel CDKL5 transcripts coding isoforms characterized by an altered C-terminal region strongly questions the eventual pathogenicity of sequence variations located in the 3'-end of the gene.

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Rett syndrome (RTT) is a neurodevelopmental disorder caused by MECP2 mutations. Previous studies performed on Mecp2-deficient brain showed striking changes in neuronal maturation. We recently showed that MeCP2 deficiency affects microtubule (MT) dynamics in RTT astrocytes.

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Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by mutations in the gene MECP2 encoding the methyl-CpG binding protein 2. This genetic disease affects predominantly girls and is characterized by a period of normal development that lasts for 8-18 months, followed by neurologic regression affecting both motor and mental abilities. Previous studies performed on brains from RTT subjects and Mecp2-deficient mice showed striking changes in neuronal maturation and dendritic arborization.

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