Stochasticity in response to rostrocaudal and mediolateral determinants influences inaccurate specification within kidney organoids

Abstract

BackgroundThe differentiation of human pluripotent stem cells to kidney requires the accurate recapitulation of complex morphogenetic patterning events within an in vitro environment. Current protocols are assumed to accurately pattern through intermediate mesoderm to kidney with outcomes described based on formation of recognized renal structures. However, these protocols show significant technical variability and the presence of ‘off target’ cell types. We hypothesise that such ‘off-target’ cells represent heterogeneity in commitment along predictable rostrocaudal or mediolateral axes with respect to intermediate mesoderm.ResultsTo test this hypothesis, we perform a temporal (4 stages acro..