Publications by authors named "P Arlotta"

As the field of neural organoids and assembloids rapidly expands, there is an emergent need for guidance and advice on designing, conducting and reporting experiments to increase the reproducibility and utility of these models. Here, our consortium- representing specialized laboratories from around the world- presents a framework for the experimental process that ranges from ensuring the quality and integrity of human pluripotent stem cells to characterizing and manipulating neural cells in vitro, and from transplantation techniques to considerations for modeling human development, evolution, and disease. As with all scientific endeavors, we advocate for rigorous experimental designs tailored to explicit scientific questions, and transparent methodologies and data sharing, to provide useful knowledge for both current research practices and for developing regulatory standards.

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Glioblastoma is characterized by heterogeneous malignant cells that are functionally integrated within the neuroglial microenvironment. Here, we model this ecosystem by growing glioblastoma into long-term cultured human cortical organoids that contain the major neuroglial cell types found in the cerebral cortex. Single-cell RNA-seq analysis suggests that, compared to matched gliomasphere models, glioblastoma cortical organoids (GCO) more faithfully recapitulate the diversity and expression programs of malignant cell states found in patient tumors.

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The adult hippocampus generates new granule cells (aGCs) with functional capabilities that convey unique forms of plasticity to the preexisting circuits. While early differentiation of adult radial glia-like cells (RGLs) has been studied extensively, the molecular mechanisms guiding the maturation of postmitotic neurons remain unknown. Here, we used a precise birthdating strategy to study aGC differentiation using single-nuclei RNA sequencing.

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Article Synopsis
  • Interindividual genetic variation plays a significant role in how people respond to diseases, but studying differences in human brains has been challenging due to a lack of effective models and the complexity of human cellular systems.
  • The researchers introduced "human brain Chimeroids," which are organoids created from cells of multiple donors, allowing them to represent various genetic backgrounds in a single model and capture diverse cellular lineages of the cerebral cortex.
  • The study showed that these Chimeroids could effectively evaluate how different individuals' genetic backgrounds influence their susceptibility to neurotoxic substances like ethanol and valproic acid, highlighting the potential of this model for future research in brain development and disease variation.
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Motivation: Single-cell RNA sequencing (scRNAseq) has transformed our ability to explore biological systems. Nevertheless, proficient expertise is essential for handling and interpreting the data.

Results: In this article, we present scX, an R package built on the Shiny framework that streamlines the analysis, exploration, and visualization of single-cell experiments.

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