From: Using human pluripotent stem cell models to study autism in the era of big data
Common source of variance | Examples/considerations |
---|---|
hPSC derivation | ESC versus iPSC; iPSC reprogramming methodology, donor cell type, donor age |
Culture induced genetic or epigenetic changes | Trisomies, CNVs, and SNVs acquired during reprogramming or with continued passage; X chromosome status in XX cell lines |
Human genetic variation | Influence of genetic background on expression of phenotypes; selection of related or unrelated controls, sex |
Method and timing of gene manipulation | Constitutive versus inducible; transient versus stable |
Cell types/ratios | Monolayer versus organoid; pure versus mixed brain cell types; different subtypes of excitatory neurons, inhibitory neurons, and glia |
Differentiation paradigm | Developmental patterning versus transcription factor overexpression; batch effects across differentiations |
Culture conditions | Naïve versus primed pluripotent conditions; coculture with cells from other species, with or without genetic manipulation; substrate, density, and media composition |
Time-point of analysis | Pluripotent, progenitor, or post-mitotic cell stages |