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. Author manuscript; available in PMC: 2021 Apr 12.
Published in final edited form as: Nat Cell Biol. 2020 Oct 12;22(11):1295–1306. doi: 10.1038/s41556-020-00591-9

Extended Data Fig. 8. Effect of rhBMP4 in vivo and in vitro.

Extended Data Fig. 8

(a-d) Effect of rhBMP4 treatment on fibrotic marker expression, myofibroblasts in the alveoli, weight change, and presence of ectopic SCGB1A1+ cells, in bleomycin injured C57BL/6 animals (n = 8 per group; each data point represents one animal). For (a), Col1a1 P = 0.0015; Snai1 P = 0.0769; Cdh2 P = 0.1771; Acta2 P = 0.0934; Tagln P = 0.3782.; one-tailed unpaired Student’s t-test for (a-d). Data are expressed as mean ± SD.

(e) Effect of rhBMP4 on the expression of markers of chondrogenesis, adipogenesis, and osteogenesis in the lung (n = 8 per group; each data point represents one animal). Acan P = 0.0021; Col2a1 P = 0.2363; Col10a1 P = 0.4201; Plin2 P = 0.0578; Pparg P = 0.4343; Fabp4 P = 0.0006; Spp1 P = 0.3117; Alpl P = 0.0474; Ibsp P = 0.3371; Runx2 P < 0.0001; one-tailed unpaired Student’s t-test. Data are expressed as mean ± SD.

(f) Effect of rhBMP4 on the total number of Sox2 Lin+ cells in the alveoli after bleomycin injury (n = 4 per group; each data point represents one animal; one-tailed unpaired Student’s t-test). Data are expressed as mean ± SD.

(g-i) Airway progenitor organoid co-cultured with Gli1+ mesenchyme treated with BMP4 demonstrates increased CFE and enhanced Sftpc expression with reduced Krt5 (n = 4 for solvent, n = 3 for BMP4; each data point represents one well; one-tailed unpaired Student’s t-test for (h,i)). Conversely, the BMP antagonist GREM2 acts to suppress CFE and Sftpc expression while enhancing Krt5 (n = 4 per group; each datapoint represents one well; one-tailed unpaired Student’s t-test for (h,i)). Data are expressed as mean ± SD.