Abstract
Quote:
Autism spectrum disorder (ASD) is thought to emerge during early cortical development. However, the exact developmental stages and associated molecular networks that prime disease propensity are elusive. To profile early neurodevelopmental alterations in ASD with macrocephaly, we monitored subject-derived induced pluripotent stem cells (iPSCs) throughout the recapitulation of cortical development. Our analysis revealed ASD-associated changes in the maturational sequence of early neuron development, involving temporal dysregulation of specific gene networks and morphological growth acceleration. The observed changes tracked back to a pathologically primed stage in neural stem cells (NSCs), reflected by altered chromatin accessibility. Concerted over-representation of network factors in control NSCs was sufficient to trigger ASD-like features, and circumventing the NSC stage by direct conversion of ASD iPSCs into induced neurons abolished ASD-associated phenotypes. Our findings identify heterochronic dynamics of a gene network that, while established earlier in development, contributes to subsequent neurodevelopmental aberrations in ASD.
https://www.nature.com/articles/s41593-018-0295-x- Autisic individuals have been identified to have an abnormally high number of connections among the neurons in their brains.
- Skin cells from autisic and non-autistic individuals were collected and converted to stem cells, then induced to progress into neurons (stem cell -> neural stem cell -> mature neuron).
- Cells from autistic individuals were on an accelerated RNA activity schedule compared to normal cells at the intermidiate neural stem cell stage and resulted in increased branching.
Also see
https://www.nature.com/articles/s41593-018-0287-x- Researchers forced stem cells from autistic individuals to develop into mature neurons, skipping the neural stem cell stage. This resulted in cells that looked like the ones from regular individuals.
Unfortunately, neural stem cells are specified before 3 weeks into a pregnancy, so it's unlikely that this will develop into an intervention method :( Also, autism is a spectrum disorder and may have multiple causes.