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. 2023 Oct 31;14:6909. doi: 10.1038/s41467-023-42199-1

Fig. 4. Grem1-lineage single cell transcriptomics revealed a distinct population of articular chondrocytes that can be targeted for therapy.

Fig. 4

a Single cell RNA (scRNA) sequencing data showed distinct clusters of cells isolated from the AC and GP of Grem1-TdT mice compared to Lepr-lineage cells isolated from the Lepr-TdT mice. b Heat map depicting unsupervised clustering of top 10 differentially expressed transcripts between the different clusters in a. c Grem1-lineage AC cells co-expressed genes important for AC function (Foxo1) and receptor (Fgfr3) for FGF18 treatment. One-sided chi-Square correlation analysis confirmed co-expression of Foxo1 and Fgfr3 in Grem1 expressing cells (p = 0.00113). d Experiment schema. e Representative images of fluorescent Grem1 lineage tracing in the articular joint with or without Foxo1 deletion (top) with OA lesions highlighted using red arrows, and Toluidine blue and Fast green stain (bottom) with arrows indicating cartilage lesions and chondrocyte disorganisation. n = 5 animals per group. f Percentage of Grem1-lineage ACs per HFP in control Grem1-TdT mice (circle) compared to Grem1-TdT-Foxo1 mice (square), n = 6 mice/group. g Unblinded histopathological OARSI scoring in Grem1-TdT-Foxo1 mice (square) compared to Grem1-TdT mice (circle), n = 5 mice/group. f, g bars denote st.dev. h Experimental schema. i Representative images of joints from Grem1-lineage mice with ColVII induced OA with or without FGF18 treatment with arrows indicating injury site (fluorescence, top), toluidine blue and fast green stained showing proteoglycan loss and lesions indicated by arrows (bottom). j Quantification of the percentage of Grem1-lineage cells with FGF18 treatment (left, n = 6 mice/group), OA score (middle, n = 6 mice/group) and AC thickness (right, n = 5 mice/group). Bars denote s.e.m. fj unpaired, two-tailed t test. Source data are provided as a Source Data file. Mouse image in figure schemas created with BioRender.com.