Rubella virus tropism and single cell responses in human primary tissue and microglia-containing organoids DOI Creative Commons
Galina Popova, Hanna Retallack, Chang N. Kim

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Oct. 24, 2022

Abstract Rubella virus is an important human pathogen that can cause neurologic deficits in a developing fetus when contracted during pregnancy. Despite successful vaccination programs the Americas and many developed countries, rubella remains endemic regions worldwide outbreaks occur wherever population immunity insufficient. Intense interest since was first isolated 1962 has advanced our understanding of clinical outcomes after infection disrupts key processes fetal neurodevelopment. Yet it still largely unknown which cell types brain are targeted. We show slices, predominantly infects microglia. This occurs heterogeneous but not highly microglia-enriched monoculture absence other types. By using organoid-microglia model, we further demonstrate leads to profound interferon response non-microglial cells, including neurons neural progenitor this attenuated by presence

Language: Английский

Glioblastoma evolution and heterogeneity from a 3D whole-tumor perspective DOI Creative Commons
Radhika Mathur, Qixuan Wang, Patrick G. Schupp

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(2), P. 446 - 463.e16

Published: Jan. 1, 2024

Language: Английский

Citations

78
Organoids are not organs: Sources of variation and misinformation in organoid biology DOI Creative Commons
Kim B. Jensen, Melissa H. Little

Stem Cell Reports, Journal Year: 2023, Volume and Issue: 18(6), P. 1255 - 1270

Published: June 1, 2023

In the past decade, term organoid has moved from obscurity to common use describe a 3D in vitro cellular model of tissue that recapitulates structural and functional elements vivo organ it models. The is now applied structures formed as result two distinct processes: capacity for adult epithelial stem cells re-create niche ability direct differentiation pluripotent self-organizing multicellular organogenesis. While these fields rely upon different cell types recapitulate processes, both share challenges around robustness, accuracy, reproducibility. Critically, organoids are not organs. This commentary serves discuss challenges, how they impact genuine utility, shine light on need improve standards all approaches.

Language: Английский

Citations

47
Modulation of neuronal activity in cortical organoids with bioelectronic delivery of ions and neurotransmitters DOI Creative Commons
Yunjeong Park, Sebastian Hernandez,

Cristian O. Hernandez

et al.

Cell Reports Methods, Journal Year: 2024, Volume and Issue: 4(1), P. 100686 - 100686

Published: Jan. 1, 2024

Precise modulation of brain activity is fundamental for the proper establishment and maturation cerebral cortex. To this end, cortical organoids are promising tools to study circuit formation underpinnings neurodevelopmental disease. However, ability manipulate neuronal with high temporal resolution in remains limited. overcome challenge, we introduce a bioelectronic approach control organoid selective delivery ions neurotransmitters. Using approach, sequentially increased decreased potassium (K

Language: Английский

Citations

11
Spatiotemporal expression of thyroid hormone transporter MCT8 and THRA mRNA in human cerebral organoids recapitulating first trimester cortex development DOI Creative Commons

Adina Sophie Graffunder,

Audrey Amber Julie Bresser,

Valeria Fernández Vallone

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 23, 2024

Thyroid hormones (TH) play critical roles during nervous system development and patients carrying coding variants of MCT8 (monocarboxylate transporter 8) or THRA (thyroid hormone receptor alpha) present a spectrum neurological phenotypes resulting from perturbed local TH action early brain development. Recently, human cerebral organoids (hCOs) emerged as powerful in vitro tools for disease modelling recapitulating key aspects cortex To begin exploring prospects this model thyroid research, we performed detailed characterization the spatiotemporal expression developing hCOs. Immunostaining showed membrane neuronal progenitor cell types including neuroepithelial cells, radial glia cells (RGCs), intermediate progenitors outer RGCs. In addition, detected robust protein deep layer upper neurons. Spatiotemporal SLC16A2 mRNA expression, by fluorescent situ hybridization (FISH), was highly concordant with across cortical layers. FISH already neuroepithelium before onset neurogenesis. remained low ventricular zone, increased subventricular zone whereas strong observed excitatory combination up-regulation known T3 response genes following treatment, these observations show that hCOs provide promising experimentally tractable to probe neurogenesis eventually consequences impaired function

Language: Английский

Citations

7
Rubella virus tropism and single-cell responses in human primary tissue and microglia-containing organoids DOI Creative Commons
Galina Popova, Hanna Retallack, Chang N. Kim

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 23, 2023

Rubella virus is an important human pathogen that can cause neurological deficits in a developing fetus when contracted during pregnancy. Despite successful vaccination programs the Americas and many developed countries, rubella remains endemic regions worldwide outbreaks occur wherever population immunity insufficient. Intense interest since was first isolated 1962 has advanced our understanding of clinical outcomes after infection disrupts key processes fetal neurodevelopment. Yet it still largely unknown which cell types brain are targeted. We show slices, predominantly infects microglia. This occurs heterogeneous but not highly microglia-enriched monoculture absence other types. By using organoid-microglia model, we further demonstrate leads to profound interferon response non-microglial cells, including neurons neural progenitor this attenuated by presence

Language: Английский

Citations

16
Internet-Connected Cortical Organoids for Project-Based Stem Cell and Neuroscience Education DOI Creative Commons
Matthew A.T. Elliott, H. Schweiger, Ash Robbins

et al.

eNeuro, Journal Year: 2023, Volume and Issue: 10(12), P. ENEURO.0308 - 23.2023

Published: Nov. 28, 2023

The introduction of Internet-connected technologies to the classroom has potential revolutionize STEM education by allowing students perform experiments in complex models that are unattainable traditional teaching laboratories. By connecting laboratory equipment cloud, we introduce experimentation pluripotent stem cell (PSC)-derived cortical organoids two different settings: using microscopy monitor organoid growth an introductory tissue culture course and high-density (HD) multielectrode arrays (MEAs) neuronal stimulation recording advanced neuroscience mathematics course. We demonstrate this approach develops interest both courses. All together, propose cloud as effective scalable for project-based university training.

Language: Английский

Citations

11
Exploring human brain development and disease using assembloids DOI
Sih‐Rong Wu, Tomasz J. Nowakowski

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Boosting Neurogenesis in the Adult Hippocampus Using Antidepressants and Mesenchymal Stem Cells DOI Creative Commons
Marta Kot, Pawan Kumar Neglur,

Anna Pietraszewska

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(20), P. 3234 - 3234

Published: Oct. 14, 2022

The hippocampus is one of the few privileged regions (neural stem cell niche) brain, where neural cells differentiate into new neurons throughout adulthood. However, dysregulation hippocampal neurogenesis with aging, injury, depression and neurodegenerative disease leads to debilitating cognitive impacts. These symptoms deteriorate quality life in afflicted individuals. Impaired especially difficult rescue increasing age neurodegeneration. potential boost endogenous Wnt signaling by influencing pathway modulators such as receptors, agonists, antagonists through drug therapy-based interventions offers hope. Restoration augmentation hampered facilitate increased would serve an repair mechanism contribute structural functional plasticity. This review focuses on possible interaction between under control antidepressants mesenchymal (MSCs) overcome caused age, diseases, or environmental factors stress. It will also address some current limitations hindering direct extrapolation research from animal models human application, technical challenges associated MSCs their cellular products therapeutic solutions.

Language: Английский

Citations

13
Ciliary biology intersects autism and congenital heart disease DOI Creative Commons
Nia Teerikorpi, Micaela Lasser, Sheng Wang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 31, 2024

ABSTRACT Autism spectrum disorder (ASD) commonly co-occurs with congenital heart disease (CHD), but the molecular mechanisms underlying this comorbidity remain unknown. Given that children CHD come to clinical attention by newborn period, understanding which variants carry ASD risk could provide an opportunity identify and treat individuals at high for developing far before typical age of diagnosis. Therefore, it is critical delineate subset genes most likely increase ASD. However, date there relatively limited overlap between confidence genes, suggesting alternative strategies prioritizing are necessary. Recent studies have shown gene perturbations dysregulate neural progenitor cell (NPC) biology. Thus, we hypothesized disrupt neurogenesis more Hence, performed in vitro pooled CRISPR interference (CRISPRi) screen NPC biology similarly genes. Overall, identified 45 strongly impact proliferation and/or survival NPCs. Moreover, observed a cluster physically interacting enriched ciliary Studying seven these evidence shared ( CEP290, CHD4, KMT2E, NSD1, OFD1, RFX3, TAOK1 ), observe perturbation significantly impacts primary cilia formation . While vivo investigation reveals previously unappreciated role motile development, supporting its prediction as gene. Together, our findings highlight set may underscore

Language: Английский

Citations

3
Human Brain Organoids in Migraine Research: Pathogenesis and Drug Development DOI Open Access
Parisa Gazerani

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3113 - 3113

Published: Feb. 4, 2023

Human organoids are small, self-organized, three-dimensional (3D) tissue cultures that have started to revolutionize medical science in terms of understanding disease, testing pharmacologically active compounds, and offering novel ways treat disease. Organoids the liver, kidney, intestine, lung, brain been developed recent years. used for pathogenesis investigating therapeutic options neurodevelopmental, neuropsychiatric, neurodegenerative, neurological disorders. Theoretically, several disorders can be modeled with aid human organoids, hence potential exists migraine its treatment organoids. Migraine is considered a disorder non-neurological abnormalities symptoms. Both genetic environmental factors play essential roles clinical manifestations. Several types migraines classified, example, without aura, from patients these study (e.g., channelopathy calcium channels) stressors chemical mechanical). In models, drug candidates purposes also tested. Here, limitations studying communicated generate motivation stimulate curiosity further research. This must, however, alongside complexity concept neuroethical aspects topic. Interested researchers invited join network protocol development hypothesis presented here.

Language: Английский

Citations

5