Seoul National University’s Post

Leveraging patient cell transdifferentiation into induced neurons to enhance diagnostic yield for neurological genetic disorders, Pengfei Liu, PhD, FACMGG joins this month's journal club to present this innovative workflow for rare disease diagnostics using RNA-seq. During the live journal club event, Dr. Liu will cover: 🧬How transcriptome RNA-seq using accessible tissues can fall short in characterizing genes involved in neurological disorders. 💡The streamlining of cell transdifferentiation into a diagnostic RNA-seq workflow. 🥼The increased molecular diagnostic yield by activating neurological disease-associated genes and neuron-specific isoforms with induced neuron RNA-seq. Gain these insights on June 12 by registering today: https://lnkd.in/eeH-XUHJ #ASHG #HumanGenetics

Study reveals significant differences in RNA editing between postmortem and living human brain https://lnkd.in/dP5_q8EQ Researchers have reported finding major differences between postmortem and living prefrontal cortex brain tissues as they relate to one of the most abundant RNA modifications in the brain, known as adenosine-to-inosine (A-to-I) editing.

Nova postagem: Mapping based on single-cell long-read sequencing reveals specialized splicing patterns in the brains of developing mice and adults - https://lnkd.in/du3-k5MG et al. (2024) present a comprehensive atlas of RNA isoforms in single cells from different brain regions, cell subtypes, and developmental stages in mice. Research has shown that the expression of full-length isoforms varies in 72% of genes, depending on cell type, brain region, and stage of development. The authors found that splicing, early […]

Amyotrophic lateral sclerosis (ALS) is caused by the loss of motor neurons in the brain and spinal cord, leading to muscle weakness, paralysis, and eventually death. By analyzing the genetic makeup of donated brain tissue from people who had #ALS, NINDS-funded researchers have found the culprit behind neuron death—a set of risk genes. High levels of these genes in a unique type of neuron, called the Betz cell, may trigger a chain reaction that leads to widespread neuron and glial cell dysfunction. Because Betz cells are the first to go in ALS, the findings may inform new treatment strategies to slow and even stop ALS progression. https://go.nih.gov/qrpIXjo

In this research, the authors performed snRNA-seq on over 460,000 cells from the prefrontal cortex of schizophrenia patients and healthy controls, across 140 individuals in two independent cohorts. They found that excitatory neurons were mostly affected, particularly in neurodevelopment and synapse-related molecular pathways. Additionally, numerous important transcription factors (TFs), etiological genetic risk factors, and differentially expressed genes (DEGs) related to schizophrenia were identified. Finally, the authors discovered that the clinical diagnoses of patients and healthy controls were not consistent with transcriptional studies. This research has several advantages. Firstly, the extensive snRNA-seq of over 460,000 cells includes many neuronal subtypes. Secondly, the identified DEGs, TFs, and genetic risk factors are valuable for understanding the mechanisms of schizophrenia. Thirdly, their findings in comparing the transcripts of patients and healthy individuals provide valuable information for clinical studies. Lastly, a series of cutting-edge computational analysis tools were applied in this research. Paper link: https://lnkd.in/eRk4Ygri #TiwariLab #JournalClub

Genome-wide association studies (GWASs) have identified numerous loci linked to neurodevelopmental and psychiatric disorders, but understanding the specific target genes and biological mechanisms remains a major challenge. Here Wen et al provide a comprehensive analysis of genetic regulation across diverse ancestries, focusing on gene expression, isoform variation, and splicing in brain development. By integrating multi-ancestry datasets, the study highlights how genetic diversity influences brain development at multiple molecular levels. This cross-ancestry approach advances our understanding of neurodevelopmental processes, revealing ancestry-specific regulatory mechanisms and their potential links to neurological disorders. The atlas serves as a valuable resource for future research, emphasizing the importance of including diverse populations in genetic studies to capture a broader spectrum of human biology. However future studies should focus on including more diverse populations and the atlas could also be applied to studying age-specific or region-specific gene regulation patterns in the brain, potentially informing personalized medicine and therapies for brain-related diseases. Paper link: https://lnkd.in/dBthciZ3 #TiwariLab #JournalClub

Human brains are a complex network of cells with intricate interactions. New research from scientists at the University of California, San Diego, sheds light on how genetic components impact cellular function as brain cells age. The study reveals that certain brain cells age more rapidly in individuals with Alzheimer’s disease and demonstrates sex-specific differences in cell aging processes. The findings, detailed in a Nature paper titled, “Single-cell multiplex chromatin and RNA interactions in aging human brain,” highlight the importance of understanding these nuances for potential therapeutic interventions. Find the Nature paper linked below! #alzheimers #singlecell #RNA

📃Scientific paper: WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice Abstract: Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-022-00997-5. Continued on ES/IODE ➡️ https://etcse.fr/qzeBd ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice Abstract: Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-022-00997-5. Continued on ES/IODE ➡️ https://etcse.fr/qzeBd ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice Abstract: Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-022-00997-5. Continued on ES/IODE ➡️ https://etcse.fr/qzeBd ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.