scOpen untangles kidney fibrosis
Improved analysis, precision in research
scATAC-seq allows the examination of accessible DNA regions in single cells. However, the nature of the experimental protocol makes it difficult to reliably analyze and interpret the data. Researchers from the e:Med junior research alliance Fibromap have developed the scOpen tool to analyze these single-cell data in more detail. Their tool leads to a better understanding of renal fibrosis and uncovered a previously unknown role of the Runx1 gene in the progression of this disease.
Fibrosis is the scarring of organ tissue. Often associated with disfunction, it is a hallmark of many chronic and metabolic diseases such as Chronic Kidney Disease (CKD). Dissecting the complex genetic and molecular interactions that lead to fibrosis is a crucial first step towards finding better diagnostics and ultimately to development of suitable therapeutic strategies against CKD. Researchers of e:Med junior research alliance Fibromap have developed a computational tool to analyse single-cell data in a more precise manner. Their tool leads to better understanding of fibrosis and uncovered a previously unknown role for gene Runx1 in fibrotic progression. An in-depth understanding of fibrotic tissue can be achieved by investigating genomic and epigenomic state of individual cells with methods such as “Single-cell Assay for Transposase Accessible Chromatin using sequencing” (scATAC-seq).
scATAC-seq data is used to determine the accessible regions of DNA in individual cells. However, the nature of the experimental protocol makes it difficult to reliably analyse and interpret the data. The team of Professor Ivan Costa (RWTH Aachen) therefore developed a computational tool, scOpen, which gives better estimations on open chromatin states of the cells and ultimately improves analysis and interpretation of scATAC-seq data. scOpen performed better than existing computational tools. scOpen improved downstream data analysis and led to detection of cell types and cell-regulatory changes during kidney fibrosis. When the scientists applied scOpen on data from kidney fibrosis mouse models, they revealed an unknown role of Runx1. This gene caused differentiation of fibroblasts to myofibroblasts after kidney injury. This finding was confirmed by molecular staining in mice and overexpression assays in human fibroblast cell lines. Concurring herewith Runx1 deficiency led to a decrease in myofibroblast formation. Understanding how fibrosis progresses in kidneys is an important step towards development of therapeutic strategies. The highly complex nature of the fibrosis, coupled with complicated experimental set-ups make it challenging to address the issue. scOpen provides a more reliable way to interpret data. The example of Runx1 in fibrotic progression proves its value. Inhibition of this gene can be used to prevent the formation of scar tissue and can thus be explored as possible therapeutic strategy for CKD patients.
Li, Z., C. Kuppe, S. Ziegler, M. Cheng, N. Kabgani, S. Menzel, M. Zenke, R. Kramann and I. G. Costa (2021). "Chromatin-accessibility estimation from single-cell ATAC-seq data with scOpen." Nat Commun 12(1): 6386. Fibromap doi.org/10.1038/s41467-021-26530-2.
Junior research alliance and contact:
Prof. Dr. Ivan Costa, RWTH Aachen