Intrinsic vs dimensionality-dependent origin of symmetry-breaking and scaling in organoids

Determine whether symmetry-breaking and size-scaling in pluripotent stem cell-derived organoids, particularly two-dimensional adherent gastruloids formed from micropatterned pluripotent stem cell colonies under differentiation-inducing conditions, emerge intrinsically from self-organizing mechanisms or require higher-dimensional tissue organization (for example, three-dimensional gastruloids or equivalent multicellular architectures) to generate spatial asymmetry and scaling behavior.

Background

Organoid systems recapitulate aspects of early embryogenesis and are used to probe pattern formation, symmetry-breaking, and growth control. While spontaneous axial polarization has been observed in three-dimensional gastruloids, asymmetries have not been reported in two-dimensional adherent gastruloids, raising uncertainty about the role of dimensionality.

The paper investigates mesodermal pattern formation in 2D gastruloids using quantitative imaging and a Turing activator–repressor model with reactive boundaries. The explicit open question concerns whether the observed symmetry-breaking and scaling behaviors arise intrinsically in 2D or instead require the organizational complexity inherent to higher-dimensional tissues.