Molecular determinants of nephron vascular specialization in the kidney

David M. Barry, Elizabeth A. McMillan, Balvir Kunar, Raphael Lis, Tuo Zhang, Tyler Lu, Edward Daniel, Masataka Yokoyama, Jesus M. Gomez-Salinero, Angara Sureshbabu, Ondine Cleaver, Annarita Di Lorenzo, Mary E. Choi, Jenny Xiang, David Redmond, Sina Y. Rabbany, Thangamani Muthukumar, Shahin Rafii

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number5705
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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