Purpose Of Review: Applying discoveries from basic research to patients in the neonatal intensive care unit (NICU) is challenging given the difficulty of modeling this population in animal models, lack of translational relevance from animal models to humans, and scarcity of primary human tissue. Human cell-derived cerebral organoid models are an appealing way to address some of these gaps. In this review, we will touch on previous work to model neonatal conditions in cerebral organoids, some limitations of this approach, and recent strategies that have attempted to address these limitations.
Recent Findings: While modeling of neurodevelopmental disorders has been an application of cerebral organoids since their initial description, recent studies have dramatically expanded the types of brain regions and disease models available. Additionally, work to increase the complexity of organoid models by including immune and vascular cells, as well as modeling human heterogeneity with mixed donor organoids will provide new opportunities to model neonatal pathologies.
Summary: Organoids are an attractive model to study human neurodevelopmental pathologies relevant to patients in the neonatal ICU. New technologies will broaden the applicability of these models to neonatal research and their usefulness as a drug screening platform.
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http://dx.doi.org/10.1097/MOP.0000000000001446 | DOI Listing |
J Am Chem Soc
March 2025
Leibniz Forschungsinstitut für Molekulare Pharmakologie, Campus Berlin-Buch, 13125 Berlin, Germany.
Monoacylglycerol lipase (MAGL) is the pivotal catabolic enzyme responsible for signal termination in the endocannabinoid system. Inhibition of MAGL offers unique advantages over the direct activation of cannabinoid receptors in treating cancer, metabolic disorders, and inflammatory diseases. Although specific fluorescent molecular imaging probes are commonly used for the real-time analysis of the localization and distribution of drug targets in cells, they are almost invariably composed of a linker connecting the pharmacophore with a large fluorophore.
View Article and Find Full Text PDFHeterozygous loss-of-function (LoF) variants in a transcription factor known to play key roles in ciliogenesis, result in autism spectrum disorder (ASD) and neurodevelopmental delay. RFX binding motifs are also enriched upstream of genes found to be commonly dysregulated in transcriptomic analyses of brain tissue from individuals with idiopathic ASD. Still, the precise functions of in the human brain is unknown.
View Article and Find Full Text PDFSingle-cell transcriptomics has revolutionized our understanding of neurodevelopmental cell identities, yet, predicting a cell type's developmental state from its transcriptome remains a challenge. We perform a meta-analysis of developing human brain datasets comprising over 2.8 million cells, identifying both tissue-level and cell-autonomous predictors of developmental age.
View Article and Find Full Text PDFMitotic spindle orientation is crucial for cell fate determination and tissue organization. Although the intracellular machinery governing spindle orientation is well characterized, whether and how secreted factors, such as morphogens, regulate this process remains poorly understood. This study investigated the role of Hedgehog (HH) signaling in modulating mitotic spindle orientation in neural progenitor cells and in induced pluripotent stem cells (iPSCs).
View Article and Find Full Text PDFSci Adv
March 2025
Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are primarily genetic in ~20% of patients. Mutations in are the most frequent cause, but it is not understood why there is notable regional pathology. An increased burden of mitochondrial DNA (mtDNA) mutations in ALS-FTLD brains implicates mitochondrial mechanisms; however, it remains unclear how and when these mutations arise.
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