A fluctuation test for gastruloid heterogeneity.

Heritable fluctuations in mouse embryonic stem cell states are a key source of heterogeneity in monoclonal gastruloids, with more related cells producing more similar organoids.

• Why it matters: Understanding the origins of organoid heterogeneity is crucial for improving developmental models and regenerative medicine, yet the sources of variability remain unclear.
• What they did: The study generated monoclonal gastruloids from single mESCs and used DNA Typewriter to trace cell lineages, revealing heritable fate biases and gene expression differences linked to developmental potential.
• The result: Findings suggest intrinsic, heritable fluctuations in stem cell states influence organoid diversity, and DNA Typewriter provides detailed lineage trees that can inform stem cell-based research.