Fig. 7: A patient-specific iPSC BRICHOS SFTPC mutation AT2 model reveals AT2 unfolded protein response and emergence of an intermediate epithelial state gene signature. | Nature Communications

Fig. 7: A patient-specific iPSC BRICHOS SFTPC mutation AT2 model reveals AT2 unfolded protein response and emergence of an intermediate epithelial state gene signature.

From: Aberrant intermediate alveolar epithelial cells promote pathogenic activation of lung fibroblasts in preclinical fibrosis models

Fig. 7

a Schematic of mutant (SFTPCC121Y/tdT) and corrected (SFTPCWT/tdT) syngeneic iPSC clone development. b Graph showing iAT2 yield per input cell at each passage for mutant and corrected clones. Two-way Student’s t test at each passage; n = 4 biological replicates at P1 and n = 6 biological replicated at P2-4. c Immunofluorescent staining of mutant and corrected iAT2 alveolospheres for proSP-C shows reticular pattern in mutant proSP-C and punctate pattern in corrected proSP-C (representative of n = 3 biological replicates). d Western blotting of iAT2 lysates for proSP-C, mature SP-C and UPR marker proteins BIP and CHOP (n = 3 biological replicates). e UMAP projection of iAT2 scRNAseq from mutant and corrected iAT2s showing genotype-based segregation. f Violin plots of UPR genes DDIT3 (CHOP) and HSPA5 (BIP) in mutant and corrected iAT2s. Two-way Student’s t test. g (left) UMAP projection and (right) violin plot of UPR gene score. Welch two-way Student’s t test. h Densitometry analysis from (d) of BIP and CHOP protein (n = 3 biological replicates). Two-way Student’s t test. i Violin plots of intermediate cell state genes KRT7, CLDN4, and KRT19 in mutant and corrected iAT2s. Two-way Student’s t test. j (left) UMAP projection and (right) violin plot of KRT5-/KRT17+ aberrant basaloid gene score14. Welch two-way Student’s t test. k (left) UMAP projection and (right) violin plot of TGF-β gene score17. Welch two-way Student’s t test. l RT-qPCR gene expression of TGFB1, CDKN1A and (m) FGFR2 in corrected and mutant iAT2s (n = 3 biological replicates). Two-way Student’s t test. b, h, l, m Data are presented as median value± range. g, j, k Box plot within violin display the median (center line), the first and third quartiles (box limits), and whiskers indicating the minimum and maximum values within 1.5 times the interquartile range. Source data are provided as a Source Data file. p value is shown if p  <  0.05. Schematics Created in BioRender. Rodriguez, L. (2025) https://BioRender.com/deg4vtp.

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