Researchers at The Ohio State University Wexner Medical Center have performed a meta-analysis of all induced pluripotent stem cell models for neurological and neurodegenerative diseases, and created an atlas of how cell characteristics are linked to their genotype.
Their research is published online today in EMBO Molecular Medicine.
"Synthesizing this information to understand the phenotypic role of disease-promoting genes and identifying the limitations of our current practices will be crucial steps toward achieving the great translational potential of induced pluripotent stem cell models of neurological diseases," said Dr. Jaime Imitola, director of the Progressive Multiple Sclerosis Multidisciplinary Clinic and Translational Research Program at Ohio State.
A decade after the discovery of iPSCs, hundreds of patient cell lines and neurological disease phenotypes have been generated. Yet this abundance of phenotypic information has become difficult to follow and interpret, and research practices for iPSC neurological disease modeling varies among different laboratories, Imitola said.
For this study, researchers included 93 out of more than 110 studies initially screened, from which they collected data on phenotypes and genotypes, encompassing 31 neurological diseases that span the pediatric to adult population with a total of 71 gene mutations. As they analyzed the correlation of 663 neuronal phenotypes with genotypic data from 243 patients and 214 controls, and examined research practices and reporting bias in neurological disease models, they found that there is no established standard for the reporting of methods nor a defined minimal number of cell lines.
From the retrospective analysis of the published literature, researchers developed a taxonomy of central nervous system cellular phenotypes in vitro, and revealed that there are previously unrelated genes that show similar disease phenotypes. This work also showed that alterations in patient-derived cells at the level of gene expression correlate with the reported cellular phenotypes, and these dysregulated genes are highly expressed in specific regions of disease in the human brain.
The iPS cell phenogenetic map project atlas (iPhemap), an open submission, online database, will be open for researchers to query and deposit phenotypic information of neurological diseases.