Anatomically matched spatial comparisons identify Trps1 as a regulator of knee interzone formation
Abstract
How the interzone forms and gives rise to articular cartilage, ligaments, and synovium is incompletely understood. Using our previously generated spatial and single-cell transcriptomic atlas of the mouse hindlimb, we compared the knee interzone with neighboring tissues and with the ankle interzone at matched positions, and identified Trps1 as a knee interzone-enriched candidate. Pseudotime analysis placed Trps1-high cells in a transitional state between chondrogenic progenitors and matrix-producing chondrocytes, with higher chondrogenic and lower fibroblastic program scores. Targeted Trps1 knockdown in hindlimb explants disrupted joint formation, permitted Col2a1 expression within the interzone, and reduced adjacent cartilage formation. The associated chondrogenic program was conserved in the human embryonic knee, whereas TRPS1 expression in osteoarthritic cartilage was associated with a fibroblastic matrix program. These results support a role for Trps1 in knee interzone development and show that anatomically matched spatial comparison with explant perturbation can nominate and test joint regulators.
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BibTeX
@misc{cahan2026anatomically,
title = {{Anatomically matched spatial comparisons identify Trps1 as a regulator of knee interzone formation}},
author = {Patrick Cahan and Ji-hye Yea and Sharon E.S. Onggo and Haneul Cho Cho},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.28.762640},
url = {https://www.biorxiv.org/content/10.64898/2026.10.28.762640v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Anatomically matched spatial comparisons identify Trps1 as a regulator of knee interzone formation
AU - Patrick Cahan
AU - Ji-hye Yea
AU - Sharon E.S. Onggo
AU - Haneul Cho Cho
PY - 2026
DA - 2026/10/28
PB - bioRxiv
DO - 10.64898/2026.10.28.762640
UR - https://www.biorxiv.org/content/10.64898/2026.10.28.762640v1
AB - How the interzone forms and gives rise to articular cartilage, ligaments, and synovium is incompletely understood. Using our previously generated spatial and single-cell transcriptomic atlas of the mouse hindlimb, we compared the knee interzone with neighboring tissues and with the ankle interzone at matched positions, and identified Trps1 as a knee interzone-enriched candidate. Pseudotime analysis placed Trps1-high cells in a transitional state between chondrogenic progenitors and matrix-producing chondrocytes, with higher chondrogenic and lower fibroblastic program scores. Targeted Trps1 knockdown in hindlimb explants disrupted joint formation, permitted Col2a1 expression within the interzone, and reduced adjacent cartilage formation. The associated chondrogenic program was conserved in the human embryonic knee, whereas TRPS1 expression in osteoarthritic cartilage was associated with a fibroblastic matrix program. These results support a role for Trps1 in knee interzone development and show that anatomically matched spatial comparison with explant perturbation can nominate and test joint regulators.
SN - 2692-8205
ER -