Spectral Signatures Reveal a Transient Commitment Bottleneck During Pancreatic Endocrine Differentiation

Single-cell transcriptomics reconstructs developmental trajectories, but quantitative frameworks for population-level transcriptional reorganization during lineage commitment remain underdeveloped, limiting systems-level insights into cell fate specification. Here we introduce a spectral framework based on singular value decomposition of the cell-by-gene expression matrix, applied to murine pancreatic endocrine development (GSE132188). We derive two collective observables: R _eff , the effective number of active modes quantifying the dimensionality of collective transcriptional states, and R ₃ , a third-order statistic measuring mode-weight distribution asymmetry. Along pseudotime, endocrine differentiation exhibits a transient R _eff minimum at the Ngn3 -high state, marking a low-dimensional population-wide commitment bottleneck. R ₃ rises during Fev  + and terminal differentiation, reflecting asymmetric stabilization of lineage-specific regulatory programs during fate diversification. A random-order null model reduces these signatures, confirming they reflect coherent developmental progression rather than sampling effects. The leading eigenmodes recover biologically interpretable transcriptional programs underlying progenitor-to-mature endocrine progression and transient endocrine commitment. Together, these results support cell-fate specification as an ordered, collective reorganization in high-dimensional expression-state space, and demonstrate that physics-inspired spectral observables complement standard single-cell trajectory analysis to uncover system-level developmental principles.