Genetics play a prominent role in autism, as nearly 1,000 genes have been nominated as contributors in the form of point mutations, single gene deletions and chromosomal rearrangements1. These genes play many different roles in the developing human brain, yet somehow all contribute to the same core set of neurobehavioral traits. The points of molecular and cellular convergence across these genes are unknown, and their elucidation could dramatically improve drug discovery efforts and clinical trial designs. Limitations in traditional experimental animal and in vitro models have made it difficult to investigate numerous autism risk factors at once.
However, recent advancements in stem cell technologies have enabled researchers to generate neural cells from patient-derived stem cells in a rapid and efficient manner, thus creating the substrate for large-scale functional human genomics experiments. Michael F. Wells and colleagues have developed a new tool called a “cell village” that simultaneously characterizes the molecular profiles and cellular traits of many donor cell lines that have been cultured in the same in vitro environment2.
Coupled with their rapid neural cell models and bioinformatic approaches, Wells and his team plan to use cell villages to identify the relationships among genes, expression and cellular behaviors at an unprecedented scale while minimizing the technical variation typical of arrayed designs (i.e., one donor per well). They aim to leverage these new technologies to profile the transcriptional and cellular phenotypes of induced pluripotent stem cell (iPSC)-derived neural cells from neurotypical and autistic individuals harboring mutations in 11 different high-confidence autism genes with the intent of detecting shared disease mechanisms across these genetic states. Collectively, this work could lead to an improved understanding of the origins of autism and the development of therapeutics that are effective in a greater proportion of individuals with autism.