Here, we present a protocol for using Brain and Organoid Manifold Alignment (BOMA), a cloud-based web app for comparative gene expression data analysis between brains and organoids. We describe steps for performing a global alignment of developmental gene expression data from both brains and organoids. We then detail procedures for investigating both shared and distinctive developmental pathways across brains and organoids by refining alignment locally using manifold learning. This protocol is applicable for working with single-cell and bulk RNA sequencing data. For complete details on the use and execution of this protocol, please refer to He et al..
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http://dx.doi.org/10.1016/j.xpro.2024.103375 | DOI Listing |
Sci Adv
January 2025
Department of Medical Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Protein translation is crucial for fear extinction, a process vital for adaptive behavior and mental health, yet the underlying cell-specific mechanisms remain elusive. Using a Tet-On 3G genetic approach, we achieved precise temporal control over protein translation in the infralimbic medial prefrontal cortex () during fear extinction. In addition, our results reveal that the disruption of cytoplasmic polyadenylation element binding protein 1 (Cpeb1) leads to notable alterations in cell type-specific translational programs, thereby affecting fear extinction.
View Article and Find Full Text PDFNeuro Oncol
January 2025
Childhood Cancer & Cell Death team (C3 team), Consortium South-ROCK, LabEx DEVweCAN, Institut Convergence Plascan, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, 69008 Lyon, France.
Background: Brain tumors are the deadliest solid tumors in children and adolescents. Most of these tumors are glial in origin and exhibit strong heterogeneity, hampering the development of effective therapeutic strategies. In the past decades, patient-derived tumor organoids (PDT-O) have emerged as powerful tools for modeling tumoral cell diversity and dynamics, and they could then help defining new therapeutic options for pediatric brain tumors.
View Article and Find Full Text PDFCommun Biol
January 2025
Department of Neurodegenerative Diseases, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd, Duarte, CA, 91010, USA.
Brain organoid models have greatly facilitated our understanding of human brain development and disease. However, key brain cell types, such as microglia, are lacking in most brain organoid models. Because microglia have been shown to play important roles in brain development and pathologies, attempts have been made to add microglia to brain organoids through co-culture.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Beckman Research Institute of City of Hope, Duarte, CA, USA
Background: Brain organoid models were generated from healthy control or Alzheimer’s disease patient iPSCs to facilitate our understanding of AD pathogenesis.
Method: ApoE3 and ApoE4 iPSCs were developed into brain organoids using our recently developed brain organoid platform that allows prolonged culture of brain organoids. Human iPSCs were also differentiated into microglia, which were then co‐cultured with brain organoids.
Alzheimers Dement
December 2024
Neural Stem Cell Institute, Rensselaer, NY, USA
Background: Human pluripotent stem cell (hPSC)‐derived brain organoids patterned towards the cerebral cortex are valuable models of interactions occurring in cortical tissue. We and others have used these cortical organoids to model dominantly inherited FTD‐tau. While these studies have provided essential insights, cortical organoid models have yet to reach their full potential.
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