Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo

Chiaradia, Ilaria; Lancaster, Madeline A.

doi:10.1038/s41593-020-00730-3

Cited by 215 publications

(157 citation statements)

References 150 publications

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“…Advances in 3D modeling including extracellular matrix composition, optimized media transitions and agitation of the tissues led to the formation of cerebral organoids with various brain region identities. These advances revealed the remarkable fidelity with which organogenesis can occur in vitro leading to accurate modeling of events occurring during the first half of gestation in humans (reviewed in Chiaradia and Lancaster, 2020). While cerebral organoids are capable to spontaneously acquired forebrain, midbrain and hindbrain identities, it is feasible to generate particular brain regions of interest by applying novel modified protocols for guiding and directing regional identity (Kadoshima et al, 2013;Pasca et al, 2015;Tanaka et al, 2020).…”

Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

“…While cerebral organoids are capable to spontaneously acquired forebrain, midbrain and hindbrain identities, it is feasible to generate particular brain regions of interest by applying novel modified protocols for guiding and directing regional identity (Kadoshima et al, 2013;Pasca et al, 2015;Tanaka et al, 2020). Brain organoids recapitulate many features of the fetal human brain, including cytoarchitecture, cell diversity and maturation and comprise a variety of cell types comparable, to some extent, to the complex composition of the cells present in the brain (reviewed in Chiaradia and Lancaster, 2020). Importantly, spontaneous neuronal activity has been detected in brain organoids suggesting the existence of functional communication among neuronal cells (Lancaster et al, 2013).…”

Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

“…Importantly, spontaneous neuronal activity has been detected in brain organoids suggesting the existence of functional communication among neuronal cells (Lancaster et al, 2013). Brain organoids have been used for modeling neurological diseases and NDDs, providing remarkable advantage in studying diseases in vitro, in a 3D environment resembling the affected tissue (reviewed in Chiaradia and Lancaster, 2020). The position of organoids at the interface of in vitro and in vivo neurobiology makes them a unique model system that will provide further progress in understanding brain development (Chiaradia and Lancaster, 2020).…”

Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

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SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis

Stevanović

Drakulić

Lazic

et al. 2021

Front. Mol. Neurosci.

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

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Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

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SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis

Stevanović

Drakulić

Lazic

et al. 2021

Front. Mol. Neurosci.

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“…Nevertheless, they are progressively becoming powerful tools to study neural cell biology in species where neural tissue is scarce or unavailable [9][10][11][12].…”

Section: Accepted Articlementioning

confidence: 99%

From stem and progenitor cells to neurons in the developing neocortex: key differences among hominids

2021

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Stem cells and neurons in the hominid neocortex Abbreviations: neural stem and progenitor cells (NSPCs), million years ago (mya), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), ventricular zone Accepted Article This article is protected by copyright. All rights reserved (VZ), neuroepithelial cells (NECs), apical radial glia (aRG), apical progenitors (APs), subventricular zone (SVZ), inner and outer SVZ (ISVZ and OSVZ), basal progenitors (BPs), neuroepithelial (NE), basal radial glia (bRG)

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“…Moreover, a human specific gene, ARHGAP11B, has recently been shown to promote the enhanced proliferative capacity of human basal cortical progenitors by augmenting a specific metabolic pathway (Namba et al 2020 As in other vertebrate embryos, the extracellular environment, including spatially and temporally regulated signals provided by neighbouring tissues, is likely to orchestrate human embryonic differentiation. In vitro models, from rosettes to more complex three-dimensional organoids and gastruloids, aim to recreate this by provision of supportive extracellular environments and timely exposure to ligands or small molecules that modulate signalling activity (Lancaster et al 2013, Otani et al 2016, Ogura et al 2018, Chiaradia and Lancaster 2020, Moris et al 2020. A critical test of the extent to which neural progenitor differentiation is governed by cell autonomous mechanisms is their behaviour in a heterologous environment.…”

Section: Introductionmentioning

confidence: 99%

Human spinal cord differentiation proceeds rapidly in vitro and only initially maintains differentiation pace in a heterologous environment

Dady

Davidson

Halley

et al. 2021

Preprint

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Species-specific differentiation pace in in vitro assays indicates that some aspects of neural differentiation are driven by cell-autonomous processes. Here we describe a novel in vitro human neural rosette assay that recapitulates the temporal sequence of dorsal spinal cord differentiation but proceeds more rapidly than in the human embryonic spinal cord, suggesting that in vitro conditions lack endogenous signalling dynamics. To test the extent to which this in vitro assay represents a cell intrinsic differentiation programme, human iPSC-derived neural rosettes were homo-chronically grafted into the faster differentiating chicken embryonic neural tube. Strikingly, in vitro human differentiation pace was not accelerated, even in single host-integrated cells. Moreover, rosette differentiation eventually stalled in a neural progenitor cell state. These findings demonstrate the requirement for timely extrinsic signalling to accurately recapitulate human neural differentiation tempo, and suggest that while intrinsic properties limit differentiation pace, such signals are also required to maintain differentiation progression

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Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo

Cited by 215 publications

References 150 publications

SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis

SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis

From stem and progenitor cells to neurons in the developing neocortex: key differences among hominids

Human spinal cord differentiation proceeds rapidly in vitro and only initially maintains differentiation pace in a heterologous environment

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