Fig. 6: Human A-ICs, but not other kidney subtypes, have differential leading biological pathways following UPEC exposure and phagosome maturation is a leading A-IC subtype biological pathway.

The ten leading biological pathways ranked by p-value are presented and the colored box beside the cell type corresponds to the cluster color in Fig. 1. a With saline exposure, cluster 0/A-IC subtype A, nuclear factor, erythroid 2-like 2 (NRF2)-mediated oxidative stress response, phagosome maturation, and antigen presentation were the 3 leading biological pathways. With UPEC exposure, cluster 0/A-IC subtype A, phagosome maturation surpassed NRF-mediated oxidative stress response to become the leading pathway. TNF receptor superfamily member 4 (OX40) signaling and cell division cycle 42 (Cdc42) signaling appeared in the top ten pathways. b Cluster 3/A-IC subtype B also had differential rankings of the ten most involved pathways. Phagosome maturation moved from the fourth to third most involved pathway and Cdc42 signaling, OX40 signaling, and ketogenesis replaced xenobiotic metabolism, T-cell exhaustion signaling, and aldosterone signaling in epithelial cells as the eighth, ninth, and tenth most involved pathways with UPEC compared to saline exposure. c Cluster 5/A-IC subtype C was the remaining cell type that had differential top ten involved pathways between saline and UPEC exposure. Ketolysis moved from fourth to second, aryl hydrocarbon response went from glutathione-mediated detoxification appearing with UPEC-replacing sirtuin signaling pathway that moved off of the list. a–c Data were analyzed using IPA (QIAGEN Inc., https://www.qiagenbioinformatics.com/products/ingenuity-pathway-analysis). IPA reports a p value using a right-tailed Fisher’s exact test. d “IC reporter” mice were challenged with UPEC strain CFT073 or saline transurethrally for 1 h. ICs were flow-sorted and Atp6v1b1 mRNA expression was analyzed. Atp6v1b1 mRNA expression increased by a median average of ~2-fold (35.23 (20.40–67.17) saline vs. 73.40 (51.97–115.00)) (UPEC) in ICs following transurethral inoculation of UPEC strain CFT073 versus saline; n = 11 mice in saline and n = 12 mice in UPEC group. Statistical significance (asterisk) between saline and UPEC exposure was determined by the Mann–Whitney test because the data were not parametric. The results are presented as the median and interquartile range. Source data are provided as a Source Data File.