Anatomically matched spatial comparisons identify Trps1 as a regulator of knee interzone formation

Trps1 is enriched in the mouse knee interzone and marks a transitional cell state between chondrogenic progenitors and matrix-producing chondrocytes.

• Why it matters: Interzone formation and how it generates joint tissues remains incompletely understood, limiting identification of regulators that can be tested in joint development.
• What they did: Using a spatial and single-cell transcriptomic atlas of the mouse hindlimb, anatomically matched comparisons with neighboring and ankle interzone tissues nominated Trps1; targeted Trps1 knockdown in hindlimb explants assessed effects on joint formation.
• The result: Trps1 knockdown disrupted joint formation, allowed Col2a1 expression within the interzone, and reduced adjacent cartilage formation, while the chondrogenic program was conserved in the human embryonic knee.

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