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Molecular determinants of nephron vascular specialization in the kidney.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Barry DM,McMillan EA,Kunar B,Lis R,Zhang T,Lu T,Daniel E,Yokoyama M,Gomez-Salinero JM,Sureshbabu A,Cleaver O,Di Lorenzo A,Choi ME,Xiang J,Redmond D,Rabbany SY,Muthukumar T,Rafii S

doi

10.1038/s41467-019-12872-5

subject

Has Abstract

pub_date

2019-12-13 00:00:00

pages

5705

issue

1

issn

2041-1723

pii

10.1038/s41467-019-12872-5

journal_volume

10

pub_type

杂志文章

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