Antiviral immunity within neural stem cells distinguishes viral strain differences in forebrain organoids DOI
Christine Vazquez, Seble G. Negatu,

Carl Bannerman

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Авг. 20, 2024

Abstract Neural stem cells have intact innate immune responses that protect them from virus infection and cell death. Yet, viruses can antagonize such to establish neuropathogenesis. Using a forebrain organoid model system at two developmental time points, we identified neural cells, in particular radial glia, are basally primed respond by upregulating several antiviral interferon-stimulated genes. Infection of these organoids with neuropathogenic Enterovirus-D68 strain, demonstrated the ability this impede activation blocking interferon responses. Together, our data highlight gene signatures present different types differential viral capacity block neural-specific induction.

Язык: Английский

Modelling human brain development and disease with organoids DOI
Marcella Birtele, Madeline A. Lancaster, Giorgia Quadrato

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 12, 2024

Язык: Английский

Процитировано

13

From organoids to organoids-on-a-chip: Current applications and challenges in biomedical research DOI Creative Commons
Kailun Liu,

Xiaowei Chen,

Zhen Fan

и другие.

Chinese Medical Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Abstract The high failure rates in clinical drug development based on animal models highlight the urgent need for more representative human biomedical research. In response to this demand, organoids and organ chips were integrated greater physiological relevance dynamic, controlled experimental conditions. This innovative platform—the organoids-on-a-chip technology—shows great promise disease modeling, discovery, personalized medicine, attracting interest from researchers, clinicians, regulatory authorities, industry stakeholders. review traces evolution organoids-on-a-chip, driven by necessity advanced biological models. We summarize applications of simulating pathological phenotypes therapeutic evaluation technology. section highlights how integrating technologies chips, such as microfluidic systems, mechanical stimulation, sensor integration, optimizes organoid cell types, spatial structure, functions, thereby expanding their applications. conclude addressing current challenges offering insights into prospects. advancement is poised enhance fidelity, standardization, scalability. Furthermore, integration cutting-edge interdisciplinary collaborations will be crucial progression

Язык: Английский

Процитировано

1

Advances in the knowledge and therapeutics of schizophrenia, major depression disorder, and bipolar disorder from human brain organoid research DOI Creative Commons
Rosa Villanueva

Frontiers in Psychiatry, Год журнала: 2023, Номер 14

Опубликована: Июль 12, 2023

Tridimensional cultures of human induced pluripotent cells (iPSCs) experimentally directed to neural differentiation, termed “brain organoids” are now employed as an in vitro assay that recapitulates early developmental stages nervous tissue differentiation. Technical progress culture methodology enabled the generation regionally specialized organoids with structural and neurochemical characters distinct encephalic regions. The technical process organoid elaboration is undergoing progressively implementation, but current robustness has attracted attention psychiatric research substitute/complement animal experimentation for analyzing pathophysiology disorders. Numerous morphological, structural, molecular functional insights disorders have been uncovered by comparing brain made iPSCs obtained from control healthy subjects patients. Brain were also response conventional treatments, search new drugs, anticipate therapeutic individual patients a personalized manner. In this review, we gather data studying cerebral three most frequent serious disorders: schizophrenia, major depression disorder, bipolar disorder. Among these studies, emphasize: (i) origin pathologies takes place embryonic development; (ii) existence shared pathogenic aspects among disorders; (iii) occurrence differences between bearing same (iv) alterations can be activated or aggravated environmental signals genetic risk

Язык: Английский

Процитировано

12

Brain organoids: A new tool for modelling of neurodevelopmental disorders DOI Creative Commons
Yirizhati Aili, Nuersimanguli Maimaitiming, Zengliang Wang

и другие.

Journal of Cellular and Molecular Medicine, Год журнала: 2024, Номер 28(17)

Опубликована: Сен. 1, 2024

Abstract Neurodevelopmental disorders are mostly studied using mice as models. However, the mouse brain lacks similar cell types and structures those of human brain. In recent years, emergence three‐dimensional organoids derived from embryonic stem cells or induced pluripotent allows for controlled monitoring evaluation early neurodevelopmental processes has opened a window studying various aspects development. such lack original anatomical structure during maturation, maturation that rely on unique cellular interactions neural network connections limited. Consequently, difficult to be used extensively effectively while modelling later stages development disease progression. To address this problem, several methods technologies have emerged aim enhance sophisticated regulation developmental through bioengineering approaches, which may alleviate some current limitations. This review discusses advances application areas organoid culture methods, aiming generalize optimization strategies systems, improve ability mimic development, value organoids.

Язык: Английский

Процитировано

3

Antiviral immunity within neural stem cells distinguishes Enterovirus-D68 strain differences in forebrain organoids DOI Creative Commons
Christine Vazquez, Seble G. Negatu,

Carl Bannerman

и другие.

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Ноя. 5, 2024

Neural stem cells have intact innate immune responses that protect them from virus infection and cell death. Yet, viruses can antagonize such to establish neuropathogenesis. Using a forebrain organoid model system at two developmental time points, we identified neural cells, in particular radial glia, are basally primed respond by upregulating several antiviral interferon-stimulated genes. Infection of these organoids with neuropathogenic Enterovirus-D68 strain, demonstrated the ability this impede activation blocking interferon responses. Together, our data highlight gene signatures present different types differential viral capacity block neural-specific induction.

Язык: Английский

Процитировано

3

Two independent translocation modes drive neural stem cell dissemination into the human fetal cortex DOI Creative Commons
Ryszard Wimmer,

Pauline Lestienne,

Christοphe Brunet

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Abstract The strong size increase of the human neocortex is supported both by amplification and basal translocation a neural stem cell population, radial glial cells (or bRG cells). Using live imaging second trimester fetal tissue cortical organoids, we identify two independent modes for colonization neocortex. On top an actomyosin-dependent movement called mitotic somal (MST), microtubule-dependent motion occurring during interphase, that call interphasic (IST). We show IST driven LINC complex, through nuclear envelope recruitment dynein motor its activator LIS1. Consequently, severely altered in LIS1 patient-derived organoids. also demonstrate MST occurs prometaphase spindle event. controlled rounding molecular pathway, via Moesin Vimentin, driving translocation. report 85% due to IST, total 0,67 mm per month gestation. Our work identifies how colonize cortex, further shows are conserved bRG-related migrating glioblastoma cells.

Язык: Английский

Процитировано

0

Using cortical organoids to understand the pathogenesis of malformations of cortical development DOI Creative Commons
Kellen D. Winden,

Isabel Gisser,

Mustafa Şahin

и другие.

Frontiers in Neuroscience, Год журнала: 2025, Номер 18

Опубликована: Янв. 15, 2025

Malformations of cortical development encompass a broad range disorders associated with abnormalities in corticogenesis. Widespread neuronal formation or migration can lead to small head size microcephaly disorganized placement cell types. Specific, localized malformations are termed focal dysplasias (FCD). Neurodevelopmental common all types the most prominent being refractory epilepsy, behavioral such as autism spectrum disorder (ASD), and learning disorders. Several genetic pathways have been these from control cycle cytoskeletal dynamics global variants growth factor signaling pathways, especially those interacting mechanistic target rapamycin (mTOR), FCDs. Despite advances understanding disorders, underlying developmental that lesion mechanisms through which defects cause specific neurological symptoms often remains unclear. One limitation is difficulty modeling animal models frequently do not faithfully mirror human phenotype. To circumvent this obstacle, many investigators turned three-dimensional stem brain, known organoids, because they recapitulate early neurodevelopmental processes. High throughput analysis organoids presents promising opportunity model pathophysiological processes across breadth development. In review, we highlight pathophysiology brain using organoid models.

Язык: Английский

Процитировано

0

Emerging approaches to enhance human brain organoid physiology DOI Creative Commons
Anna Pagliaro, Benedetta Artegiani, Delilah Hendriks

и другие.

Trends in Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Brain organoids are important 3D models for studying human brain development, disease, and evolution. To overcome some of the existing limitations that affect organoid quality, reproducibility, characteristics, in vivo resemblance, current efforts directed to improve their physiological relevance by exploring different, yet interconnected, routes. In this review, these approaches latest developments discussed, including stem cell optimization, refining morphogen administration strategies, altering extracellular matrix (ECM) niche, manipulating tissue architecture mimic morphogenesis. Additionally, strategies increase diversity enhance maturation, such as establishing co-cultures, assembloids, xenotransplantation, reviewed. We explore how various factors can be tuned intermingled speculate on future avenues towards even more physiologically-advanced organoids.

Язык: Английский

Процитировано

0

Modeling forebrain regional development and connectivity by human brain organoids DOI

Mu Seog Choe,

Cynthia Lo,

In‐Hyun Park

и другие.

Current Opinion in Genetics & Development, Год журнала: 2025, Номер 91, С. 102324 - 102324

Опубликована: Фев. 20, 2025

Язык: Английский

Процитировано

0

Epigenetic and metabolic regulation of developmental timing in neocortex evolution DOI Creative Commons

Matilde Aquilino,

Nora Ditzer, Takashi Namba

и другие.

Trends in Neurosciences, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

The human brain is characterized by impressive cognitive abilities. neocortex the seat of higher cognition, and expansion a hallmark evolution. While developmental programs are similar in different species, timing transitions capacity neural progenitor cells (NPCs) to proliferate differ, contributing increased production neurons during cortical development. Here, we review epigenetic regulation corticogenesis, focusing mostly on humans while building knowledge from studies mice. We discuss metabolic-epigenetic interplay as potential mechanism integrate extracellular signals into chromatin. Moreover, synthesize current understanding how metabolic deregulation can cause neurodevelopmental disorders. Finally, outline be investigated using organoid models.

Язык: Английский

Процитировано

0