ABSTRACT
The biology and diversity of glomerular parietal epithelial cells (PECs) are important for understanding podocyte regeneration and crescent formation. Although protein markers have revealed the morphological heterogeneity of PECs, the molecular characteristics of PEC subpopulations remain largely unknown. Here, we performed a comprehensive analysis of PECs using single-cell RNA sequencing (scRNA-seq) data. Our analysis identified five distinct PEC subpopulations: PEC-A1, PEC-A2, PEC-A3, PEC-A4 and PEC-B. Among these subpopulations, PEC- A1 and PEC-A2 were characterized as podocyte progenitors while PEC-A4 represented tubular progenitors. Further dynamic signaling network analysis indicated that activation of PEC-A4 and the proliferation of PEC-A3 played pivotal roles in crescent formation. Analyses suggested that upstream signals released by podocytes, immune cells, endothelial cells and mesangial cells serve as pathogenic signals and may be promising intervention targets in crescentic glomerulonephritis. Pharmacological blockade of two such pathogenic signaling targets, proteins Mif and Csf1r, reduced hyperplasia of the PECs and crescent formation in anti-glomerular basement membrane glomerulonephritis murine models. Thus, our study demonstrates that scRNA-seq-based analysis provided valuable insights into the pathology and therapeutic strategies for crescentic glomerulonephritis.
Subject(s)
Glomerulonephritis , Kidney Diseases , Podocytes , Mice , Animals , Endothelial Cells/pathology , Epithelial Cells/metabolism , Kidney Glomerulus/pathology , Podocytes/pathology , Glomerulonephritis/pathology , Proteins/metabolism , Kidney Diseases/pathologyABSTRACT
PURPOSE: The purpose of the study was to provide quantitative information about the facial soft-tissue characteristics of operated unilateral complete cleft lip and palate (UCCLP) children compared with healthy children during mixed dentition. METHODS: Lateral cephalometric radiographs of 48 children with UCCLP who had been operated on before the age of 2 years were analyzed and compared with those of a control group of 60 healthy children with the same age, sex, and ethnic characteristics. RESULTS: The children with operated UCCLP differed from the control group by having a more concave profile, flatter nasal tip, more retrognathic basis nasi, shorter upper lip, thicker upper and lower lip, reduced upper-lip projection, and increased lower-lip projection. CONCLUSIONS: The facial soft-tissue morphology in operated UCCLP patients differed from normal controls of the same age, sex, and ethnic group. It may be necessary for children with UCCLP operated before 2 years of age to have some preventive treatment.