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Table 1 Examples of common sources of variance in hPSC models

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