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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

Figure 3. Mesenchymal Hh activation promotes metaplastic KRT5 differentiation while suppressing SFTPC differentiation from airway.

Figure 3.

(a,b) Histology quantification of areas of KRT5+ pods and percentage of SFTPC+ cells after constitutive Hh activation (activation with SmoM2) in Gli1+ cells followed by bleomycin injury (n = 9 per group; each data point represents one animal; one-tailed unpaired Student’s t-test). Data are expressed as mean ± SD.

(c-e) Histology quantification of areas of KRT5+ pods and percentage of SFTPC+ cells and oximetry after Hh inactivation (deletion of Smo) in Gli1+ cells followed by bleomycin injury (n = 7 for control, n = 9 for Hh-inactivated; each data point represents one animal; one-tailed unpaired Student’s t-test for (d,e)). Data are expressed as mean ± SD.

(f-i) CFE, organoid size, and composition of airway progenitors co-cultured with Gli1 Lin+ mesenchyme isolated from Hh-activated fibrotic lungs compared to Gli1 Lin+ mesenchyme from control fibrotic lung (n = 5 per group for (h), n = 3 per group for (i); each data point represents one well; one-tailed unpaired Student’s t-test for (h,i)). Data are expressed as mean ± SD.

(j) Model of Hh activation in the Gli1+ mesenchyme acting in trans to promote SOX2+ progenitor differentiation into metaplastic KRT5+ basal cells. Data are expressed as mean ± SD. Hh = hedgehog. Scale bars, 100 µm.