About this Research Topic
Neuropsychiatric conditions, such as autism and schizophrenia, are challenging to model using stem cell-derived brain organoids; an in-vitro laboratory model that can recapitulate critical stages of early human brain development that cannot be detected using other methods, such as post-mortem brain tissue or animal models. This is because of the following two reasons: (1) Behavioural phenotypes defining neuropsychiatric conditions are subtle. This means that a condition does not have a clear neurological trait such as microcephaly or macrocephaly, and an organoid model often cannot adequately recapitulate the subtle neurological changes that alter behaviour; (2) Genetic backgrounds of such conditions are often complex and multifactorial. This means when a condition manifests due to mutations in multiple genes, elucidating the transcriptional and regulatory effects of these mutations is often a time-consuming process.
Early research using brain organoid models have been critical in understanding species-specific processes that stimulate brain growth and complexity in humans, making it an invaluable developmental biology tool. However, like all model systems, brain organoids are prone to generating biological artefacts resulting in limited scope for clinical research; major research groups have focussed primarily on understanding typical brain development using standardised embryonic stem cells (ESCs) or a limited cohort of induced pluripotent stem cells (iPSCs) from tissue donors.
However, recent advances in single cell technologies have provided insights into the biological artefacts of brain organoid culture and subtle variations associated with brain organoids from different stem cell lines. This has created a foundation for studies into neuropsychiatric conditions. We are now able to implement single cell methods to study subtle phenotypes that define most neuropsychiatric conditions. Further, we have also made improvements in induced pluripotent stem cell (iPSC) derivation methods, which has significantly improved stem cell-based differentiation methods, using tissue from independent donor cohorts around the world.
Together these advancements have made brain organoids a hugely successful model for human development, giving rise to a third challenge – the moral and ethical concerns of tissue donors who may perceive personal connection with organoids grown from their tissue.
Against this backdrop, this research topic seeks two types of contributions:
(1) To test the validity of using stem cell derived brain organoids especially from induced pluripotent stem cells, in discovering the biological basis of neuropsychiatric conditions, such as but not limited to:
a. Autism
b. Schizophrenia
c. Attention deficit hyperactivity disorder
d. Bipolar disorder
(2) To review the field of stem cell-derived brain organoid ethics towards addressing moral and ethical concerns of tissue donors, and to create an informed consent framework that works for tissue donors, biobanks, and commercial parties.
Early research using brain organoid models have been critical in understanding species-specific processes that stimulate brain growth and complexity in humans, making it an invaluable developmental biology tool. However, like all model systems, brain organoids are prone to generating biological artefacts resulting in limited scope for clinical research; major research groups have focussed primarily on understanding typical brain development using standardised embryonic stem cells (ESCs) or a limited cohort of induced pluripotent stem cells (iPSCs) from tissue donors.
However, recent advances in single cell technologies have provided insights into the biological artefacts of brain organoid culture and subtle variations associated with brain organoids from different stem cell lines. This has created a foundation for studies into neuropsychiatric conditions. We are now able to implement single cell methods to study subtle phenotypes that define most neuropsychiatric conditions. Further, we have also made improvements in induced pluripotent stem cell (iPSC) derivation methods, which has significantly improved stem cell-based differentiation methods, using tissue from independent donor cohorts around the world.
Together these advancements have made brain organoids a hugely successful model for human development, giving rise to a third challenge – the moral and ethical concerns of tissue donors who may perceive personal connection with organoids grown from their tissue.
Against this backdrop, this research topic seeks two types of contributions:
(1) To test the validity of using stem cell derived brain organoids especially from induced pluripotent stem cells, in discovering the biological basis of neuropsychiatric conditions, such as but not limited to:
a. Autism
b. Schizophrenia
c. Attention deficit hyperactivity disorder
d. Bipolar disorder
(2) To review the field of stem cell-derived brain organoid ethics towards addressing moral and ethical concerns of tissue donors, and to create an informed consent framework that works for tissue donors, biobanks, and commercial parties.
Keywords: brain organoids, autism, schizophrenia, attention deficit hyperactivity disorder, bipolar disorder, ethics, tissue donors, neuropsychiatric conditions, neurodevelopment
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
