Alomone Labs’ Post

3D Model Brains from Multiple Donors: Key Insights 🧠 Innovative Brain Models Researchers have developed 3D brain organoids using cells from multiple donors, with the aim to reveal individual variations in brain development and drug responses. #BrainModels #Organoids 🔬 Chimeroid Technology These "Chimeroids" combine cells from up to five donors, potentially from hundreds in the future, enhancing genetic diversity in brain studies. #Chimeroids #GeneticDiversity 👩🔬 Drug Response Testing This model could predict individual responses to new therapeutics, providing a powerful tool for personalised medicine. #PersonalisedMedicine #DrugTesting 📚 Methodology The approach involves creating single-donor organoids, which are then homogenized and pooled to form composite organoids, enabling detailed neurophysiological and molecular studies. #ResearchMethods #Neuroscience Altogether, it looks very labor intensive and will be great to 'multiplex' starting donor cells so one can backtrack differences in response to treatment. It may also allow one to have different n number replicates in one go! Source: https://lnkd.in/emk7vpVn Image source: Antón-Bolaños et al./Nature

𝗛𝘂𝗺𝗮𝗻 𝗕𝗿𝗮𝗶𝗻 𝗖𝗵𝗶𝗺𝗲𝗿𝗼𝗶𝗱𝘀 𝗶𝗻 𝗗𝗶𝘀𝗲𝗮𝘀𝗲 𝗥𝗲𝘀𝗲𝗮𝗿𝗰𝗵 - 𝗔𝗻 𝘂𝗽𝗱𝗮𝘁𝗲 𝘁𝗼 𝘁𝗵𝗶𝘀 𝗍𝗁𝖾𝗆𝖾 𝗳𝗿𝗼𝗺 𝗮 𝗉𝗈𝗌𝗍 𝖿𝗋𝗈𝗆 𝗳𝗲𝘄 𝘄𝗲𝗲𝗸𝘀 𝗮𝗴𝗼! A important survey finds that regulatory concerns are a major barrier to the adoption of non-animal testing models in research and development. Despite advances in alternative newer and increasingly more relevant in vitro methods, these models face significant challenges in gaining regulatory acceptance. #NonAnimalTesting #RegulatoryAffairs #R&D Read more here: https://lnkd.in/gxUncYXh 👌 A good work around that should be promoted: A new paper in Nature (https://lnkd.in/e7Dv7QiZ) shows that mixing cells from different individuals can help bypass the need for running different numbers at once.... Human Brain Chimeroids in Disease Research: 🧠 New Adapted Brain Model: Chimeroids, created by co-developing cells from multiple donors, replicate human brain development, allowing for diverse genetic representation. #Neuroscience #Innovation 🧪 Genetic Variation Study: This model investigates how genetic differences affect brain cell response to neurotoxins like ethanol or drugs such as valproic acid, showing variability in susceptibility among the same cells which came from different individuals. #Genetics #Research 🔬 High-Throughput Analysis: Chimeroids are a scalable system for examining individual differences in brain development and disease processes, enhancing our understanding of genetic impacts on health. #Bioinformatics #DiseaseResearch Such newer technologies will fuel research results with wider relevance and takes into account personalised medicine without having to resort to in vivo models.

Cutting-edge advancements in both live-cell imaging and AI have revolutionized the approach to cell segmentation and live/dead classification, offering unparalleled insights into cellular health under true physiological conditions. Join us July 9th at 7 am PDT for a must-see webinar exploring: ✅ How an integrated AI-driven approach provides accurate measurements of proliferation across a range of cell types ✅ Validation of label-free analysis methods for robustly quantifying cell health in a non-perturbing manner ✅ Demonstration of a simplified workflow combining AI-driven and fluorescent quantification for the high-throughput screening of therapeutic compounds ✅ Guidance on how live-cell imaging and intuitive label-free analysis can be built into your development workflow Register now: https://ow.ly/1chm50SkwNy #LiveCellAnalysis #Cytotoxicity #Oncology #Neuroscience

🧠 4 posters to check out at SfN this week My colleagues Jeroen, Shushant, Peter, and Debbie are in Chicago right now for the annual meeting of the Society for Neuroscience! Find them at booth 368 to see how Ncardia can help you de-risk drug discovery with iPSC-derived models. You can also learn more in these posters: 🔶 Evaluation of human induced pluripotent stem cell (hiPSC)-derived tri-culture as in vitro model for Alzheimer’s Disease Board B60; In-Person Presentation Time: Sun., Oct. 6, 1-2pm. 🔶 Cellular and Molecular Mechanisms of Tauopathies, Synucleinopathies, and Other Degenerative Diseases Board C7; In-Person Presentation Time: Tue., Oct. 8, 10-11am 🔶 Leveraging an hiPSC-derived 3D tri-culture model to accelerate neuronal maturation and induce microglial dysfunction in a model of tauopathy Board B134; In-Person Presentation Time: Tue., Oct. 8, 10-11am 🔶 Development of iPSC-based Parkinson’s disease model for drug discovery Board B139; In-Person Presentation Time:  Tue., Oct. 8, 4-5pm #sfn2024 #neuroscience #drugdiscovery #ipsc

You’ll see CD9, or Cluster of Differentiation 9, in a lot of processes, like cell signaling, adhesion, migration, and even immune responses. It’s also an excellent exosome marker 👓 This Microscopy Monday we’re looking at the Anti-CD9 (extracellular) Antibody that lets you easily look at CD9 expression whatever your research focus is. And because it only targets the extracellular part of CD9, it’s excellent for flow cytometry and live cell work. As well as being a known marker of exosomes (aka extracellular vesicles), CD9 plays a role in T cell activation, B cell regulation, and allergic mediator release from mast cells. You’ll also find it in the central nervous system, where it’s important for neurite outgrowth, cell migration, and making sure neurons have a working myelin sheath. So it’s an interesting protein to look at! On the left below, you can see CD9 expression in perfusion-fixed frozen mouse hippocampus sections. It’s stained with our Anti-CD9 (extracellular) Antibody (ANR-209) and visible in green thanks to goat anti-rabbit-AlexaFluor-488. You can CD9 in the pyramidal layer (P). On the right, we’ve pre-incubated the antibody with CD9 (extracellular) Blocking Peptide (BLP-NR209), which suppresses staining and serves as an excellent control. Cell nuclei are stained blue with DAPI. Take a look at the rest of the data here: https://lnkd.in/e9H2Ecwn #exosomes #extracellularVesicles #neuroscience #immunohistochemistry #antibodies

New study introduces a screening method for identifying drugs that modulate the reactivity of astrocytes, cells implicated in neurodegeneration due to disease, injury, and aging. Histone deacetylase 3 (HDAC3) inhibitors were found to effectively reduce harmful astrocyte responses. The inhibitor RGFP966 specifically prevented the formation of reactive astrocytes and promoted neuroprotection in mouse models, highlighting the therapeutic potential of targeting astrocyte reactivity in neurodegenerative conditions. #Neurodegeneration #AstrocyteModulation #HDAC3Inhibitors #Neuroprotection #BiomedicalResearch #Neuroscience #TherapeuticStrategies https://lnkd.in/ei23Txdx

Microglia Rescue Neurons from Aggregate-Induced Neuronal Dysfunction & Death   Microglia are crucial for maintaining brain health and neuron function. In a recent publication in Neuron they report that microglia establish connections with neurons using tunneling nanotubes (TNTs) in both physiological and pathological conditions. These TNTs facilitate the rapid exchange of organelles, vesicles, and proteins. In neurodegenerative diseases like Parkinson’s and Alzheimer’s disease, toxic aggregates of alpha-synuclein (α-syn) and tau accumulate within neurons. Our research demonstrates that microglia use TNTs to extract neurons from these aggregates, restoring neuronal health. Additionally, microglia share their healthy mitochondria with burdened neurons, reducing oxidative stress and normalizing gene expression. Disrupting mitochondrial function with antimycin A before TNT formation eliminates this neuroprotection. Moreover, co-culturing neurons with microglia and promoting TNT formation rescues suppressed neuronal activity caused by α-syn or tau aggregates. Notably, TNT-mediated aggregate transfer is compromised in microglia carrying Lrrk22(Gly2019Ser) or Trem2(T66M) and (R47H) mutations, suggesting a role in the pathology of these gene variants in neurodegenerative diseases.   Highlights: Alpha-synuclein (α-syn) & tau trigger tunneling nanotube formation between microglia & neuron Tunneling nanotubes facilitate the relocation of α-syn and tau into microglia Microglia donate healthy mitochondria to α-syn- and tau-burdened neurons Exchange of mitochondria rescues neurons from oxidative stress & dysfunction   Read the full publication: https://lnkd.in/dHSkK7yu   #neuroscience #microglia #alphasynuclein #mitochondrialdysfunction #tau #neurodegenerativediseases #neuroprotection #alzecure  

Check out our new study: "Single-Cell Multi-Omics Map of Cell Type-Specific Mechanistic Drivers of Multiple Sclerosis Lesions." We identified a unique genetic signature in oligodendrocytes and spatially distinct metabolic changes in astrocytes at chronic active lesions in patients with progressive multiple sclerosis. Read more here: https://lnkd.in/eXfF2vXp #MultipleSclerosis #Neuroscience #SingleCellResearch

🔬 Lab Spotlight: SG Lab 🔬 Today, we’re highlighting the interesting research at the Laboratory of Chromatin Biology and Epigenetics from Shiv Nadar Institute of Eminence 🌟 Led by Prof. Dr. Sanjeev Galande, the lab explores the molecular systems of immunology, epigenetics of regeneration, adult neurogenesis and embryonic development!✨ 🔬 Key Research Areas:🔬 Molecular Systems Immunology: The lab is interested in studying the cross-talk between such multiple signaling cascades that are important for T- cell development and differentiation.🔍🔬 Regeneration Biology: The lab works understanding epigenetic control of regeneration in Hydra.🧬🗒️ Embryonic development: The lab focuses on understanding regulation of cell fate specification and cellular movements during early embryogenesis, especially focused on gastrulation. 📊🔬 Cancer Biology: The lab works on understanding role of SATB family chromatin organizers in tumorigenesis.🦠🧬 Neuroepigenetics: The lab studies epigenetic regulation in adult neurogenesis.📈🔍 Explore more of their incredible research, visit 🔗 Lab webpage:- https://lnkd.in/gunVesg2 ✍🏻Credits: 🎨Poster: Abhilaya Makkuva and Smrutimayee Prusty 📝Content: Abhilaya Makkuva #NGSF #LabShowcaseSeries #embryogenesis #epigenetics #cancerbiology #neuroscience #NGSF

🧬✨ Unlocking Alzheimer's Secrets: How BHLHE40/41 Regulates Our Body's Defenders in the Brain and Beyond ✨🧬 A recent study sheds new light on the genetic and experimental facets of Alzheimer's disease (AD), uncovering how certain risk alleles and genes may be influencing the way macrophages, including microglia, react to damage in lipid-rich brain tissue. 🧠💔 Leveraging advanced sc/nRNA sequencing techniques, researchers have discovered similar activation states in macrophages within aging and diseased brains, mirroring those in other lipid-afflicted tissues. These specific cell subpopulations, termed DLAMs (Damage-associated Lipid Accumulation Macrophages), are at the forefront of this groundbreaking research. 🕵️♂️🔬 The study meticulously reconstructed gene regulatory networks from macrophage data, pinpointing 11 key transcriptional regulators as potential linchpins in the DLAM response across species. 🐭👩🔬 Significantly, the reduction or loss of BHLHE40/41 transcription factors in both artificially derived microglia and human macrophages, as well as in mouse models, led to enhanced cholesterol processing and lysosomal functions. This opens up new therapeutic possibilities for AD and other diseases affecting lipid-rich tissues. 🎯💊 This collaborative effort marks a significant stride in the battle against Alzheimer's, pushing the envelope in neurodegenerative disease research and offering hope for innovative treatments. 💪🧠 link: https://lnkd.in/gUsCh5vy #AlzheimersResearch #Neuroscience #Genetics #InnovationInScience #DLAMs #BrainHealth #FightAD #ScienceCommunity