An invariant network architecture with broadly expressed regulators distinguishes cell-type from cell-state identity in situ

In zonated hepatocyte states in mouse liver, an invariant core-regulatory TF sub-network preserves identical positions and conserved interactions, while state-level CRNs differ in composition and connectivity.

• Why it matters: Cell-type CRNs are known, but it is unclear whether they reflect only cell-type identity or also change across distinct states within the same cell type.
• What they did: The study built state-level CRNs in situ using a robust LCM-Spatial-ATAC-seq workflow on microdissected hepatocyte populations, then compared shared versus state-specific network structure.
• The result: The invariant sub-network is dominated by broadly expressed TFs (with master TFs downstream), and variable peripheral networks account for about one third of interactions between states, supporting a dual cell-identity architecture.

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