Extended Data Fig. 7: Decoding upstream targets of PTH1R/ZNF521 pathway and effects of PTH1R in chondrification.

a, (Top) scATAC-seq results for ZNF521 locus in this hg38 human UCSC Genome browser window depicting E53, E57, E67, and E72 accessibility signals (vertical black lines) across cell-types and their intersections with HARs, hCONDELs, and HAQERs. Numbered blue highlighted areas depict intersections with HARs and numbered yellow highlighted areas depict intersections with hCONDELs. (Below) Zoom-in view at E53 and E57 multiomics data (accessibility on left as peaks; gene expression as horizontal violin plots on right) per cell type showing one HAR/accessibility signal intersection (broad blue highlighted area) in an intronic area of ZNF521 and three overlaps with hCONDELs. Region #2: Zoom-in view at E54 multiomics data (accessibility on left as peaks; gene expression as horizontal violin plots on right) per cell type showing HAR/accessibility signal intersection (blue highlighted area with an asterisk) in the intron of ZNF521 present in smooth muscle progenitors and mesenchymal cells. b, CT scans and histological differences of Wildtype vs PTH1R humanized mouse pelves at P21 and E15.5 (bottom row). c, (Left) scATAC-seq results for upstream targets of PTH1R in the hg38 human UCSC Genome browser window depicting E53, E57, E67, and E72 accessibility signals (vertical black lines) across cell-types and their intersections with HARs, hCONDELs, and HAQERs. Blue highlighted areas depict intersections with HARs. (Right) Zoom-in view at E53 and E57 multiomics data (accessibility on left as peaks; gene expression as horizontal violin plots on right) per cell type showing HAR/accessibility signal intersection (broad blue highlighted area) in IGF1 and no HAR/hCONDEL/HAQER intersections at IHH and WNT7A. Abbreviations: AC, acetabulum; HZ, hypertrophic zone; IL, ilium; PZ, proliferative zone.