Lewy Body-like Pathology and Loss of Dopaminergic Neurons in Midbrain Organoids Derived from Familial Parkinson’s Disease Patient DOI Creative Commons
Andrea Becerra-Calixto, Abhisek Mukherjee, Santiago Ramírez

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 625 - 625

Published: Feb. 15, 2023

Progressive accumulation of α-Synuclein (αSyn) in Lewy bodies (LBs) and loss dopaminergic (DA) neurons are the hallmark pathological features Parkinson’s disease (PD). Although currently available vitro vivo models have provided crucial information about PD pathogenesis, mechanistic link between progressive αSyn into LBs DA is still unclear. To address this, it critical to model LB formation neuron loss, two key neuropathological aspects PD, a relevant system. In this study, we developed human midbrain-like organoid (hMBO) PD. We demonstrated that hMBOs generated from induced pluripotent stem cells (hiPSCs), derived familial (fPD) patient carrying gene (SNCA) triplication accumulate over time. These cytoplasmic inclusions spatially morphologically resembled diverse stages were composed markers LBs. Importantly, was paralleled by elevated apoptosis. The study will complement existing provide unique platform spatiotemporal events governing their relation with neurodegeneration. Furthermore, also be beneficial for screening development therapeutic compounds.

Language: Английский

A guide to the organ-on-a-chip DOI Creative Commons
Chak Ming Leung, Pim de Haan, Kacey Ronaldson-Bouchard

et al.

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: May 12, 2022

Organs-on-chips (OoCs) are systems containing engineered or natural miniature tissues grown inside microfluidic chips. To better mimic human physiology, the chips designed to control cell microenvironments and maintain tissue-specific functions. Combining advances in tissue engineering microfabrication, OoCs have gained interest as a next-generation experimental platform investigate pathophysiology effect of therapeutics body. There many examples there applications, making it difficult for new researchers understand what makes one OoC more suited an application than another. This Primer is intended give introduction aspects that need be considered when developing application-specific OoC. The covers guiding principles considerations design, fabricate operate OoC, well subsequent assaying techniques extract biological information from devices. Alongside this discussion current future applications technology, inform design operational decisions during implementation systems. with aim mimicking physiology range biomedical therapeutic applications. Leung, de Haan et al. report practical tips organ-on-a-chip

Language: Английский

Citations

631
Genomics, convergent neuroscience and progress in understanding autism spectrum disorder DOI
Helen Rankin Willsey, A. Jeremy Willsey, Belinda Wang

et al.

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(6), P. 323 - 341

Published: April 19, 2022

Language: Английский

Citations

145
Functional neuronal circuitry and oscillatory dynamics in human brain organoids DOI Creative Commons
Tal Sharf, Tjitse van der Molen, Stella M.K. Glasauer

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 29, 2022

Human brain organoids replicate much of the cellular diversity and developmental anatomy human brain. However, physiology neuronal circuits within remains under-explored. With high-density CMOS microelectrode arrays shank electrodes, we captured spontaneous extracellular activity from derived induced pluripotent stem cells. We inferred functional connectivity spike timing, revealing a large number weak connections skeleton significantly fewer strong connections. A benzodiazepine increased uniformity firing patterns decreased relative fraction weakly connected edges. Our analysis local field potential demonstrate that contain assemblies sufficient size to co-activate generate potentials their collective transmembrane currents phase-lock spiking activity. These results point for study neuropsychiatric diseases, drug action, effects external stimuli upon networks.

Language: Английский

Citations

142
Inherited retinal diseases: Linking genes, disease-causing variants, and relevant therapeutic modalities DOI
Nina Schneider, Yogapriya Sundaresan, Prakadeeswari Gopalakrishnan

et al.

Progress in Retinal and Eye Research, Journal Year: 2021, Volume and Issue: 89, P. 101029 - 101029

Published: Nov. 25, 2021

Language: Английский

Citations

134
SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis DOI Creative Commons
Milena Stevanović, Danijela Drakulić, Andrijana Lazic

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2021, Volume and Issue: 14

Published: March 31, 2021

The SOX proteins belong to the superfamily of transcription factors (TFs) that display properties both classical TFs and architectural components chromatin. Since cloning Sox/SOX genes, remarkable progress has been made in illuminating their roles as key players regulation multiple developmental physiological processes. govern diverse cellular processes during development, such maintaining pluripotency stem cells, cell proliferation, fate decisions/germ layer formation well terminal differentiation into tissues organs. However, are not limited development since influence survival, regeneration, death control homeostasis adult tissues. This review summarized current knowledge central nervous system development. Some suspend neural progenitors proliferative, stem-like state prevent differentiation. function pioneer occupy silenced target genes keep them a poised for activation at subsequent stages At appropriate stage members maintain stemness down-regulated cells competent differentiate, while other take over functions process Distinct determine down-stream neuronal glial Thus, sequentially acting orchestrate lineage defining phenotypes. In line with crucial deregulation specific activities is associated neurodevelopmental disorders (NDDs). overview about link between gene variants NDDs presented. We outline neurogenesis brain discuss whether impaired neurogenesis, detected neurodegenerative diseases, could be activities. present data regarding interaction signaling pathways microRNAs play Finally, future research directions will improve distinct various health diseases presented discussed.

Language: Английский

Citations

120
Shell microelectrode arrays (MEAs) for brain organoids DOI Creative Commons
Qi Huang, Bo‐Hao Tang, July Carolina Romero

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(33)

Published: Aug. 17, 2022

Brain organoids are important models for mimicking some three-dimensional (3D) cytoarchitectural and functional aspects of the brain. Multielectrode arrays (MEAs) that enable recording stimulation activity from electrogenic cells offer notable potential interrogating brain organoids. However, conventional MEAs, initially designed monolayer cultures, limited contact area restricted to bottom 3D Inspired by shape electroencephalography caps, we developed miniaturized wafer-integrated MEA caps The optically transparent shells composed self-folding polymer leaflets with conductive polymer–coated metal electrodes. Tunable folding minicaps’ guided mechanics simulations enables versatile different sizes, validate feasibility electrophysiology 400- 600-μm-sized up 4 weeks in response glutamate stimulation. Our studies suggest shell MEAs great high signal-to-noise ratio spatiotemporal organoid recording.

Language: Английский

Citations

110
Brain organoid reservoir computing for artificial intelligence DOI
Hongwei Cai, Zheng Ao,

Chunhui Tian

et al.

Nature Electronics, Journal Year: 2023, Volume and Issue: 6(12), P. 1032 - 1039

Published: Dec. 11, 2023

Language: Английский

Citations

110
Microplastics exposure affects neural development of human pluripotent stem cell-derived cortical spheroids DOI
Timothy Hua, Sonia Kiran, Yan Li

et al.

Journal of Hazardous Materials, Journal Year: 2022, Volume and Issue: 435, P. 128884 - 128884

Published: April 11, 2022

Language: Английский

Citations

92
Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications DOI Creative Commons

Jonas Cerneckis,

Hongxia Cai,

Yanhong Shi

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 26, 2024

The induced pluripotent stem cell (iPSC) technology has transformed in vitro research and holds great promise to advance regenerative medicine. iPSCs have the capacity for an almost unlimited expansion, are amenable genetic engineering, can be differentiated into most somatic types. been widely applied model human development diseases, perform drug screening, develop therapies. In this review, we outline key developments iPSC field highlight immense versatility of modeling therapeutic applications. We begin by discussing pivotal discoveries that revealed potential a nucleus reprogramming led successful generation iPSCs. consider molecular mechanisms dynamics as well numerous methods available induce pluripotency. Subsequently, discuss various iPSC-based cellular models, from mono-cultures single type complex three-dimensional organoids, how these models elucidate diseases. use examples neurological disorders, coronavirus disease 2019 (COVID-19), cancer diversity disease-specific phenotypes modeled using iPSC-derived cells. also used high-throughput screening toxicity studies. Finally, process developing autologous allogeneic therapies their alleviate

Language: Английский

Citations

88
Multimodal spatiotemporal phenotyping of human retinal organoid development DOI Creative Commons
Philipp Wahle, Giovanna Brancati, Christoph Harmel

et al.

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 41(12), P. 1765 - 1775

Published: May 8, 2023

Abstract Organoids generated from human pluripotent stem cells provide experimental systems to study development and disease, but quantitative measurements across different spatial scales molecular modalities are lacking. In this study, we multiplexed protein maps over a retinal organoid time course primary adult tissue. We developed toolkit visualize progenitor neuron location, the arrangements of extracellular subcellular components global patterning in each addition, single-cell transcriptome chromatin accessibility timecourse dataset inferred gene regulatory network underlying development. integrated genomic data with spatially segmented nuclei into multimodal atlas explore ganglion cell (RGC) neighborhoods, highlighting pathways involved RGC death showing that mosaic genetic perturbations organoids insight fate regulation.

Language: Английский

Citations

75