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 and Shahin Rafii ()
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David M. Barry: Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine
Elizabeth A. McMillan: Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine
Balvir Kunar: Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine
Raphael Lis: Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine
Tuo Zhang: Genomics Resources Core Facility, Weill Cornell Medicine
Tyler Lu: Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine
Edward Daniel: University of Texas Southwestern Medical Center
Masataka Yokoyama: Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine
Jesus M. Gomez-Salinero: Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine
Angara Sureshbabu: Division of Nephrology and Hypertension, Weill Cornell Medicine
Ondine Cleaver: University of Texas Southwestern Medical Center
Annarita Di Lorenzo: Pathology and Laboratory Medicine, Weill Cornell Medicine
Mary E. Choi: Division of Nephrology and Hypertension, Weill Cornell Medicine
Jenny Xiang: Genomics Resources Core Facility, Weill Cornell Medicine
David Redmond: Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine
Sina Y. Rabbany: Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine
Thangamani Muthukumar: Division of Nephrology and Hypertension, Weill Cornell Medicine
Shahin Rafii: Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12872-5

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