Fig. 5: Scar activates Piezo1 through glycolysis fueled actomyosin contraction.
From: Scar matrix drives Piezo1 mediated stromal inflammation leading to placenta accreta spectrum
A Immunohistochemistry images of Yap localization in decidual sections proximal, or distal to scar from PAS patients; n = 3 sections; p = 0.005. B Immunofluorescence and graph showing Yap localization in dESFs on Physio and Scar; n = 3 biological replicates. p = 2 × 10−7. C RNAseq-based enrichment analysis of contractility ontologies in dESFs. D F-actin staining in dESFs on Physio, and Scar (left), n = 61 cells for each condition; p = 6 × 10−5. Graph showing length and intensity of F-actin bundles (right), n = 21 and 17 cells. p = 9 × 10−11. E Traction force map of dESFs on Physio and Scar (left). Quantification of strain energy and energy density for each cell (right); n = 50 and 82 cells; p = 0.005 and 0.01. F Time-lapse images showing Ca2+ dynamics in three individual dESFs: C1, C2, and C3; heatmap showing corresponding traction force of each cell; G Correlation analysis of energy density with Ca2+ events frequency. r: Pearson correlation coefficient; n = 27 cells. H Ca2+ events and abundance of phosphorylated RelA (I) in dESFs treated with DMSO or Blebbistatin; n = 60 and 59 cells; p = 2 × 10−6. J Concentration of IL-8 and G-CSF in supernatant of dESFs treated DMSO or Blebbistatin by ELISA; n = 3 biological samples; p = 0.002 and 0.01. K Heatmap showing gene expression of PFKs and PFKFBs in dESFs. L Images of two dESF cells showing 2-NBDG uptake (left) and their co-measured traction force maps (right). n = 50 biological replicates. M Pearson correlation analysis of cellular energy density and mean 2-NBDG intensity in dESFs; n = 50 cells. N Traction force maps and strain energy of dESFs maintained in glucose and pyruvate withmatching C molarity; n = 164 and 94 cells; p = 0.006. O Energetics profiling of oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) in dESFs at basal levels, coupled (oligomycin sensitive), and uncoupled (FCCP sensitive) respiration. n = 3 biological replicates. P dESFs on Scar show significant increase in glycolysis. n = 3 biological replicates; p = 0.03. Q Schematic showing Scar promoted cellular contractility is fueled by increased glycolysis. Data in bar graphs are showing as mean ± s.d.; statistical significance is determined by unpaired two-tailed t-test (*p < 0.05, **p < 0.01, and ****p < 0.0001; ns not significant). Source data are provided as a Source Data file. Q created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license (https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en).
