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Publication : Molecular determinants of nephron vascular specialization in the kidney.

First Author  Barry DM Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  5705
PubMed ID  31836710 Mgi Jnum  J:286694
Mgi Id  MGI:6388250 Doi  10.1038/s41467-019-12872-5
Citation  Barry DM, et al. (2019) Molecular determinants of nephron vascular specialization in the kidney. Nat Commun 10(1):5705
abstractText  Although kidney parenchymal tissue can be generated in vitro, reconstructing the complex vasculature of the kidney remains a daunting task. The molecular pathways that specify and sustain functional, phenotypic and structural heterogeneity of the kidney vasculature are unknown. Here, we employ high-throughput bulk and single-cell RNA sequencing of the non-lymphatic endothelial cells (ECs) of the kidney to identify the molecular pathways that dictate vascular zonation from embryos to adulthood. We show that the kidney manifests vascular-specific signatures expressing defined transcription factors, ion channels, solute transporters, and angiocrine factors choreographing kidney functions. Notably, the ontology of the glomerulus coincides with induction of unique transcription factors, including Tbx3, Gata5, Prdm1, and Pbx1. Deletion of Tbx3 in ECs results in glomerular hypoplasia, microaneurysms and regressed fenestrations leading to fibrosis in subsets of glomeruli. Deciphering the molecular determinants of kidney vascular signatures lays the foundation for rebuilding nephrons and uncovering the pathogenesis of kidney disorders.
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