Probing human brain evolution and development in organoids

Giandomenico, Stefano L.; Lancaster, Madeline A.

doi:10.1016/j.ceb.2017.01.001

Cited by 93 publications

(79 citation statements)

References 76 publications

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“…As mentioned, research on cerebral organoids seems to be making rapid progress both for medical applications and for probe human brain evolution and development 28. Bigger and more developed mini-brains, with a greater degree of differentiation and internal organisation, could therefore raise the ethical problems associated with the creation of life and/or acquisition of human qualities in research involving human organoids 29…”

Section: Sentient Cerebral Organoids? a Way To Assess New Ethical Quamentioning

confidence: 99%

Cerebral organoids: ethical issues and consciousness assessment

2018

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Organoids are three-dimensional biological structures grown in vitro from different kinds of stem cells that self-organise mimicking real organs with organ-specific cell types. Recently, researchers have managed to produce human organoids which have structural and functional properties very similar to those of different organs, such as the retina, the intestines, the kidneys, the pancreas, the liver and the inner ear. Organoids are considered a great resource for biomedical research, as they allow for a detailed study of the development and pathologies of human cells; they also make it possible to test new molecules on human tissue. Furthermore, organoids have helped research take a step forward in the field of personalised medicine and transplants. However, some ethical issues have arisen concerning the origin of the cells that are used to produce organoids (ie, human embryos) and their properties. In particular, there are new, relevant and so-far overlooked ethical questions concerning cerebral organoids. Scientists have created so-called mini-brains as developed as a few-months-old fetus, albeit smaller and with many structural and functional differences. However, cerebral organoids exhibit neural connections and electrical activity, raising the question whether they are or (which is more likely) will one day be somewhat sentient. In principle, this can be measured with some techniques that are already available (the Perturbational Complexity Index, a metric that is directly inspired by the main postulate of the Integrated Information Theory of consciousness), which are used for brain-injured non-communicating patients. If brain organoids were to show a glimpse of sensibility, an ethical discussion on their use in clinical research and practice would be necessary.

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Section: Sentient Cerebral Organoids? a Way To Assess New Ethical Quamentioning

confidence: 99%

Cerebral organoids: ethical issues and consciousness assessment

2018

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“…Likewise, the recent development of organoid technologies, in which neuronal tissue is able to some extent to self-organize in three dimensions and potentially reproduce some of the core circuit features of the normal brain will be important to dissect out the input-dependent and cell-intrinsic features of circuits77.…”

Section: Developmental Emergence and Plasticity Of Neocortical Circuitsmentioning

confidence: 99%

Fate and freedom in developing neocortical circuits

Jabaudon

2017

Nat Commun

106

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The activity of neuronal circuits of the neocortex underlies our ability to perceive the world and interact with our environment. During development, these circuits emerge from dynamic interactions between cell-intrinsic, genetically determined programs and input/activity-dependent signals, which together shape these circuits into adulthood. Building on a large body of experimental work, several recent technological developments now allow us to interrogate these nature–nurture interactions with single gene/single input/single-cell resolution. Focusing on excitatory glutamatergic neurons, this review discusses the genetic and input-dependent mechanisms controlling how individual cortical neurons differentiate into specialized cells to assemble into stereotypical local circuits within global, large-scale networks.

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“…). These advantages have been exploited to examine basic questions in developmental neurobiology, such as the genetic (Matsui et al, ; Mellios et al, ) and epitranscriptomic (Yoon et al, ) control of cortical neurogenesis, and to investigate evolutionary differences between human and nonhuman primate brains (Giandomenico and Lancaster, ; Mora‐Bermudez et al, ; Otani et al, ). There has also been a surge in studies modeling human genetic diseases with organoids derived from patient‐specific iPS cells and isogenic cell lines (Allende et al, ; Bershteyn et al, ; Iefremova et al, ; Lancaster et al, ; Ye et al, ).…”

Section: Translational Applications Of Brain Organoidsmentioning

confidence: 99%

Applications of Human Brain Organoids to Clinical Problems

Chen

Song

Ming

2018

Developmental Dynamics

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Brain organoids are an exciting new technology with the potential to significantly change how diseases of the brain are understood and treated. These three-dimensional neural tissues are derived from the self-organization of pluripotent stem cells, and they recapitulate the developmental process of the human brain, including progenitor zones and rudimentary cortical layers. Brain organoids have been valuable in investigating different aspects of developmental neurobiology and comparative biology. Several characteristics of organoids also make them attractive as models of brain disorders. Data generated from human organoids are more generalizable to patients because of the match in species background. Personalized organoids also can be generated from patient-derived induced pluripotent stem cells. Furthermore, the three-dimensionality of brain organoids supports cellular, mechanical, and topographical cues that are lacking in planar systems. In this review, we discuss the translational potential of brain organoids, using the examples of Zika virus, autism-spectrum disorder, and glioblastoma multiforme to consider how they could contribute to disease modeling, personalized medicine, and testing of therapeutics. We then discuss areas of improvement in organoid technology that will enhance the translational potential of brain organoids, as well as the possibility of their use as substrates for repairing cerebral circuitry after injury.

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Probing human brain evolution and development in organoids

Cited by 93 publications

References 76 publications

Cerebral organoids: ethical issues and consciousness assessment

Cerebral organoids: ethical issues and consciousness assessment

Fate and freedom in developing neocortical circuits

Applications of Human Brain Organoids to Clinical Problems

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