Emergence of a synergistic scaffold in the brains of human infants DOI Creative Commons
Thomas F. Varley, Olaf Sporns, Nathan J. Stevenson

et al.

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

Published: Feb. 23, 2024

Abstract The human brain is a complex organ comprising billions of interconnected neurons which enables interaction with both physical and social environments. Neural dynamics the whole go far beyond just sum its individual elements; property known as “synergy”. Previously it has been shown that synergy crucial for many functions cognition, however, remains unknown how when large number discrete evolve into unified system able to support synergistic interactions. Here we analysed high-density electroencephalography data from late fetal early postnatal period. We found transitions redundancy-dominated synergy-dominated around birth. Frontal regions lead emergence scaffold comprised overlapping subsystems, while integration sensory areas developed gradually, occipital central regions. Strikingly, developmental trajectories were modulated by environmental enrichment associated enhanced mother-infant interactions, level near term equivalent age was later neurocognitive development.

Language: Английский

Human fetal brain self-organizes into long-term expanding organoids DOI Creative Commons
Delilah Hendriks, Anna Pagliaro, Francesco Andreatta

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 712 - 732.e38

Published: Jan. 8, 2024

Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, solely established pluripotent stem cells. Here, we show that healthy human fetal in vitro self-organizes into (FeBOs), phenocopying aspects of vivo cellular heterogeneity and complex organization. FeBOs expanded over long time periods. FeBO growth requires maintenance integrity, which ensures production tissue-like extracellular matrix (ECM) niche, ultimately endowing expansion. lines derived different areas the central nervous system (CNS), including dorsal ventral forebrain, preserve their regional identity allow probe positional identity. Using CRISPR-Cas9, showcase generation syngeneic mutant for study cancer. Taken together, constitute complementary CNS organoid platform.

Language: Английский

Citations

36
Neural interfaces: Bridging the brain to the world beyond healthcare DOI Creative Commons
Shumao Xu,

Yang Liu,

Hyun‐Jin Lee

et al.

Exploration, Journal Year: 2024, Volume and Issue: 4(5)

Published: March 14, 2024

Abstract Neural interfaces, emerging at the intersection of neurotechnology and urban planning, promise to transform how we interact with our surroundings communicate. By recording decoding neural signals, these interfaces facilitate direct connections between brain external devices, enabling seamless information exchange shared experiences. Nevertheless, their development is challenged by complexities in materials science, electrochemistry, algorithmic design. Electrophysiological crosstalk mismatch electrode rigidity tissue flexibility further complicate signal fidelity biocompatibility. Recent closed‐loop brain‐computer while promising for mood regulation cognitive enhancement, are limited accuracy adaptability user interfaces. This perspective outlines challenges discusses progress contrasting non‐invasive invasive approaches, explores dynamics stimulation interfacing. Emphasis placed on applications beyond healthcare, highlighting need implantable high‐resolution capabilities.

Language: Английский

Citations

22
Rigor and reproducibility in human brain organoid research: Where we are and where we need to go DOI Creative Commons
Soraya O. Sandoval, Gerarda Cappuccio, Karina Kruth

et al.

Stem Cell Reports, Journal Year: 2024, Volume and Issue: 19(6), P. 796 - 816

Published: May 16, 2024

Human brain organoid models have emerged as a promising tool for studying human development and function. These preserve genetics recapitulate some aspects of development, while facilitating manipulation in an vitro setting. Despite their potential to transform biology medicine, concerns persist about fidelity. To fully harness potential, it is imperative establish reliable analytic methods, ensuring rigor reproducibility. Here, we review current analytical platforms used characterize forebrain cortical organoids, highlight challenges, propose recommendations future studies achieve greater precision uniformity across laboratories.

Language: Английский

Citations

14
Humanized brain organoids-on-chip integrated with sensors for screening neuronal activity and neurotoxicity DOI
Pelin Sağlam-Metiner, Ender Yıldırım, Can Dincer

et al.

Microchimica Acta, Journal Year: 2024, Volume and Issue: 191(1)

Published: Jan. 1, 2024

Language: Английский

Citations

11
Unraveling mechanisms of human brain evolution DOI Creative Commons
Madeline A. Lancaster

Cell, Journal Year: 2024, Volume and Issue: 187(21), P. 5838 - 5857

Published: Oct. 1, 2024

Language: Английский

Citations

11
APOE3ch alleviates Aβ and tau pathology and neurodegeneration in the human APPNL-G-F cerebral organoid model of Alzheimer’s disease DOI
Hang Liu, Fan Mei,

Rongrong Ye

et al.

Cell Research, Journal Year: 2024, Volume and Issue: 34(6), P. 451 - 454

Published: April 12, 2024

Language: Английский

Citations

8
The epilepsy–autism phenotype associated with developmental and epileptic encephalopathies: New mechanism‐based therapeutic options DOI Open Access
Nicola Specchio, Valentina Di Micco, Eleonora Aronica

et al.

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

Published: Feb. 22, 2025

Abstract Epilepsy and autism often co‐occur in genetic developmental epileptic encephalopathies (DEEs), but their underlying neurobiological processes remain poorly understood, complicating treatment. Advances molecular genetics understanding the neurodevelopmental pathogenesis of epilepsy–autism phenotype may lead to mechanism‐based treatments for children with DEEs autism. Several genes, including newly reported PPFIA3 , MYCBP2 DHX9 TMEM63B RELN are linked various disorders, intellectual disabilities, autistic features. These findings underscore clinical heterogeneity suggest diverse mechanisms influenced by genetic, epigenetic, environmental factors. Mechanisms linking epilepsy include γ‐aminobutyric acidergic (GABAergic) signaling dysregulation, synaptic plasticity, disrupted functional connectivity, neuroinflammatory responses. GABA system abnormalities, critical inhibitory neurotransmission, contribute both conditions. Dysregulation mechanistic target rapamycin (mTOR) pathway neuroinflammation also pivotal, affecting seizure generation, drug resistance, neuropsychiatric comorbidities. Abnormal function connectivity further phenotype. New treatment options targeting specific emerging. Genetic variants potassium channel genes like KCNQ2 KCNT1 frequent causes early onset DEEs. Personalized retigabine quinidine have been explored heterogeneous Efforts ongoing develop more effective KCNQ activators blockers. SCN1A variants, particularly Dravet syndrome, show potential symptoms low‐dose clonazepam, fenfluramine, cannabidiol, although human trials yet consistently replicate animal model successes. Early intervention before age 3 years, ‐ tuberous sclerosis complex‐related DEEs, is crucial. Additionally, mTOR shows promise control managing epilepsy‐associated Understanding distinct spectrum disorder implementing behavioral interventions essential improving outcomes. Despite advances, significant challenges persist diagnosing treating DEE‐associated phenotypes. Future should adopt precision health approaches improve

Language: Английский

Citations

1
The growth factor EPIREGULIN promotes basal progenitor cell proliferation in the developing neocortex DOI Creative Commons
Paula Cubillos, Nora Ditzer, Annika Kolodziejczyk

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: 43(8), P. 1388 - 1419

Published: March 21, 2024

Abstract Neocortex expansion during evolution is linked to higher numbers of neurons, which are thought result from increased proliferative capacity and neurogenic potential basal progenitor cells development. Here, we show that EREG , encoding the growth factor EPIREGULIN, expressed in human developing neocortex gorilla cerebral organoids, but not mouse neocortex. Addition EPIREGULIN increases proliferation cells, whereas ablation cortical organoids reduces subventricular zone. Treatment with promotes a further increase cells. competes epidermal (EGF) promote proliferation, inhibition EGF receptor abrogates EPIREGULIN-mediated Finally, identify putative cis-regulatory elements may contribute observed inter-species differences expression. Our findings suggest species-specific regulation expression size primates by providing tunable pro-proliferative signal

Language: Английский

Citations

7
Application Prospect of Induced Pluripotent Stem Cells in Organoids and Cell Therapy DOI Open Access
Teng Zhang, Cheng Qian,

Mengyao Song

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2680 - 2680

Published: Feb. 26, 2024

Since its inception, induced pluripotent stem cell (iPSC) technology has been hailed as a powerful tool for comprehending disease etiology and advancing drug screening across various domains. While earlier iPSC-based modeling assessment primarily operated at the cellular level, recent years have witnessed significant shift towards organoid-based investigations. Organoids derived from iPSCs offer distinct advantages, particularly in enabling observation of progression metabolism an vivo-like environment, surpassing capabilities iPSC-derived cells. Furthermore, therapy emerged focal point clinical interest. In this review, we provide extensive overview non-integrative reprogramming methods that evolved since inception iPSC technology. We also deliver comprehensive examination organoids, spanning realms nervous system, cardiovascular oncology, well systematically elucidate advancements iPSC-related therapies.

Language: Английский

Citations

5
A Survey on the Expression of the Ubiquitin Proteasome System Components HECT- and RBR-E3 Ubiquitin Ligases and E2 Ubiquitin-Conjugating and E1 Ubiquitin-Activating Enzymes during Human Brain Development DOI Open Access

Stefano Magnati,

Eugenio Alladio, Enrico Bracco

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2361 - 2361

Published: Feb. 17, 2024

Human brain development involves a tightly regulated sequence of events that starts shortly after conception and continues up to adolescence. Before birth, neurogenesis occurs, implying an extensive differentiation process, sustained by changes in the gene expression profile alongside proteome remodeling, ubiquitin proteasome system (UPS) autophagy. The latter processes rely on selective tagging with proteins must be disposed of. E3 ligases accomplish recognition target proteins. At late stage neurogenesis, take shape, neurons migrate their designated locations. After neuronal myelination and, parallel, form connections among each other throughout synaptogenesis process. Due malfunctioning UPS components, aberrant at very early stages leads neurodevelopmental disorders. Through deep data mining analysis taking advantage machine learning-based models, we mapped transcriptomic genes encoding HECT- ring-between-ring (RBR)-E3 as well E2 ubiquitin-conjugating E1 ubiquitin-activating enzymes during human development, from post-conception adulthood. inquiry outcomes unveiled some implications for neurodevelopment-related

Language: Английский

Citations

4