Fig. 3.
Transcriptomic analysis of pericytes in kidney disease. A: pericyte transdifferentiation into myofibroblasts during kidney injury is characterized by profound changes in gene expression with over 860 differentially regulated genes (false discovery rate <0.01, 549 upregulated, 313 downregulated). Normalized gene expression values are depicted as pericytes (day 0) become myofibroblasts (days 2 and 7), with the bulk of the transcriptional changes occurring by day 2. These temporal expression patterns are highly enriched in distinct functional pathways, most prominently, those involved in immunity (P value 3 × 10−48) and inflammatory response (P value 7 × 10−26) among others. Furthermore, many of the differentially expressed genes share common, overrepresented transcription factor (TF) binding sites (Bonferroni-adjusted enrichment P < 0.01), implying coordinated regulation by a limited repertoire of TFs. B: our global computational approach is amenable to more detailed data-mining analyses. For example, the cytokine interleukin-6 (Il-6) is highly upregulated when pericytes transdifferentiate into myofibroblasts, functionally maps to immune and inflammatory pathways, and has a Rela (NF-κB p65) binding site upstream of its transcription start site. Interestingly, Rela expression itself doubles when pericytes become myofibroblasts in this animal model of kidney injury.