Vascularized human cortical organoids (vOrganoids) model cortical development in vivo

Shi, Yingchao; Sun, Le; Wang, Mengdi; Liu, Jianwei; Zhong, Shaobo; Li, Rui; Li, Peng; Guo, Dadong; Ai, Fang; Chen, Ruiguo; Ge, Woo Ping; Wu, Qian; Wang, Xiaoqun

doi:10.1371/journal.pbio.3000705

Cited by 243 publications

(240 citation statements)

References 75 publications

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“…Hypothalamic tissues were then dissected under dissection microscope and subjected to tissue dissociation. The hypothalamus tissues were enzymatically digested using a papain-based dissociation protocol previously reported 69 . In short, tissues samples were dissociated into single-cell suspension by digestion buffer (1 mg ml −1 papain in hibernate E medium, Sigma).…”

Section: Methodsmentioning

confidence: 99%

Cellular and molecular properties of neural progenitors in the developing mammalian hypothalamus

et al. 2020

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The neuroendocrine hypothalamus is the central regulator of vital physiological homeostasis and behavior. However, the cellular and molecular properties of hypothalamic neural progenitors remain unexplored. Here, hypothalamic radial glial (hRG) and hypothalamic mantle zone radial glial (hmRG) cells are found to be neural progenitors in the developing mammalian hypothalamus. The hmRG cells originate from hRG cells and produce neurons. During the early development of hypothalamus, neurogenesis occurs in radial columns and is initiated from hRG cells. The radial glial fibers are oriented toward the locations of hypothalamic subregions which act as a scaffold for neuronal migration. Furthermore, we use single-cell RNA sequencing to reveal progenitor subtypes in human developing hypothalamus and characterize specific progenitor genes, such as TTYH1 , HMGA2 , and FAM107A . We also demonstrate that HMGA2 is involved in E2F1 pathway, regulating the proliferation of progenitor cells by targeting on the downstream MYBL2. Different neuronal subtypes start to differentiate and express specific genes of hypothalamic nucleus at gestational week 10. Finally, we reveal the developmental conservation of nuclear structures and marker genes in mouse and human hypothalamus. Our identification of cellular and molecular properties of neural progenitors provides a basic understanding of neurogenesis and regional formation of the non-laminated hypothalamus.

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Section: Methodsmentioning

confidence: 99%

Cellular and molecular properties of neural progenitors in the developing mammalian hypothalamus

et al. 2020

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“…An initial strategy used implantation of brain organoids in vivo , resulting in host vascularization of the engrafted organoids, organoid maturation, and prolonged survival ( Mansour et al, 2018 ). This approach has since been improved, incorporating endothelial cells to develop vascular structures in vitro prior to implantation, with implanted organoids developing more complex vasculature and integrating with host vessels, resulting in long-term survival and functional maturation ( Pham et al, 2018 ; Shi et al, 2020 ). Notably, patient-derived hiPSCs were used to generate brain organoids and endothelial cells, supporting this approach to generate patient-specific vascularized brain organoids ( Pham et al, 2018 ).…”

Section: Technological Advances For Brain Organoid Development and Chmentioning

confidence: 99%

Electrophysiological Analysis of Brain Organoids: Current Approaches and Advancements

Passaro

Stice

2021

Front. Neurosci.

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Brain organoids, or cerebral organoids, have become widely used to study the human brain in vitro. As pluripotent stem cell-derived structures capable of self-organization and recapitulation of physiological cell types and architecture, brain organoids bridge the gap between relatively simple two-dimensional human cell cultures and non-human animal models. This allows for high complexity and physiological relevance in a controlled in vitro setting, opening the door for a variety of applications including development and disease modeling and high-throughput screening. While technologies such as single cell sequencing have led to significant advances in brain organoid characterization and understanding, improved functional analysis (especially electrophysiology) is needed to realize the full potential of brain organoids. In this review, we highlight key technologies for brain organoid development and characterization, then discuss current electrophysiological methods for brain organoid analysis. While electrophysiological approaches have improved rapidly for two-dimensional cultures, only in the past several years have advances been made to overcome limitations posed by the three-dimensionality of brain organoids. Here, we review major advances in electrophysiological technologies and analytical methods with a focus on advances with applicability for brain organoid analysis.

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“…Similarly, RAB39b loss in 3D organoids has recently been shown to cause hyperproliferation and enlarged organoid size [459]. Studies are currently exploring organoid vascularization to further extend the development and complexity of these organoids [460][461][462], which will allow in the future to study more complex brain phenotypes using these in vitro approaches.…”

Section: Future Perspectivesmentioning

confidence: 99%

The emerging role of chromatin remodelers in neurodevelopmental disorders: a developmental perspective

Mossink

Negwer

Schubert

et al. 2020

Cell. Mol. Life Sci.

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Neurodevelopmental disorders (NDDs), including intellectual disability (ID) and autism spectrum disorders (ASD), are a large group of disorders in which early insults during brain development result in a wide and heterogeneous spectrum of clinical diagnoses. Mutations in genes coding for chromatin remodelers are overrepresented in NDD cohorts, pointing towards epigenetics as a convergent pathogenic pathway between these disorders. In this review we detail the role of NDD-associated chromatin remodelers during the developmental continuum of progenitor expansion, differentiation, cell-type specification, migration and maturation. We discuss how defects in chromatin remodelling during these early developmental time points compound over time and result in impaired brain circuit establishment. In particular, we focus on their role in the three largest cell populations: glutamatergic neurons, GABAergic neurons, and glia cells. An in-depth understanding of the spatiotemporal role of chromatin remodelers during neurodevelopment can contribute to the identification of molecular targets for treatment strategies.

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Vascularized human cortical organoids (vOrganoids) model cortical development in vivo

Cited by 243 publications

References 75 publications

Cellular and molecular properties of neural progenitors in the developing mammalian hypothalamus

Cellular and molecular properties of neural progenitors in the developing mammalian hypothalamus

Electrophysiological Analysis of Brain Organoids: Current Approaches and Advancements

The emerging role of chromatin remodelers in neurodevelopmental disorders: a developmental perspective

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