Rett syndrome (RTT) is a devastating disease that affects 1 in every 10,000 children born in the United States, primarily females. RTT patients undergo apparently normal development until 6-18 months of age, followed by impaired motor function, stagnation and then regression of developmental skills, hypotonia, seizures and a spectrum of autistic behaviors. Rett syndrome is a rare disease that shares certain pathways with major developmental disorders such as autism and schizophrenia, increasing the potential impact. There is no cure for Rett syndrome and the animal model does not entirely recapitulate the human disease. Thus, having the possibility to screen drugs directly in human neurons is a major milestone.
Researchers at UC San Diego have developed a novel and highly efficient method for generating astrocytes from induced pluripotent stem cells (iPSCs). Using a well-characterized rare male Rett Syndrome (RTT) patient-derived and genome-edited isogenic lines, enriched populations of cortical neurons and astrocytes were generated. RTT derived astrocytes showed significant gene expression and physiological differences compared to control cells. Co-culture experiments revealed that RTT-derived astrocyte impaired neuronal dendritic arborization and spinogenesis in control cells. In contrast, control-derived astrocytes rescued morphological RTT neuronal phenotypes. Astrocytes used in these studies were characterized by immune-staining methods, followed by plating and neuronal enrichment.
The study of autism spectrum disorder (ASD) risk variants is critical for the understanding of autism pathophysiology and related diseases. Induced pluripotent stem cells (iPSCs) provide a valuable strategy to study the effects of these variants in living patient cells. These cells are known to play a role in Parkinson’s, Alzheirmer, autism, as well as other neurological disorders and would be a useful platform for drug screening directly in human neurons.
While models have been developed for monogenic forms of ASD, no models of idiopathic ASD using iPSCs have heretofore been reported. Thus, these new iPSCs derived astrocytes provides an advancement of the current state of the art. This concept also accelerates the differentiation process reducing the time from 180 to 300 days as proposed in the literature in 30 days.
We have coverslips slides showing the success of the differentiation from stem cell to astrocytes using our defined protocol.
A PCT patent has been submitted and the technology is available for licensing.
|Patent Cooperation Treaty||Published Application||2017075271||05/04/2017||2016-105|
Pluripotent Stem Cells, autism spectrum disorder, iPSCs derived astrocytes, astrocytes, Rett syndrome, genome-edited isogenic lines