CD146+ cells are essential for kidney vasculature development

Kimmo J. Halt, Heikki E. Pärssinen, Sanna M. Junttila, Ulla Saarela, Sunder Sims-Lucas, Peppi Koivunen, Johanna Myllyharju, Susan Quaggin, Ilya N. Skovorodkin, Seppo J. Vainio*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

The kidney vasculature is critical for renal function, but its developmental assembly mechanisms remain poorly understood and models for studying its assembly dynamics are limited. Here, we tested whether the embryonic kidney contains endothelial cells (ECs) that are heterogeneous with respect to VEGFR2/Flk1/KDR, CD31/PECAM, and CD146/MCAM markers. Tie1Cre;R26RYFP-based fate mapping with a time-lapse in embryonic kidney organ culture successfully depicted the dynamics of kidney vasculature development and the correlation of the process with the CD31+ EC network. Depletion of Tie1+ or CD31+ ECs from embryonic kidneys, with either Tie1Cre-induced diphtheria toxin susceptibility or cell surface marker–based sorting in a novel dissociation and reaggregation technology, illustrated substantial EC network regeneration. Depletion of the CD146+ cells abolished this EC regeneration. Fate mapping of green fluorescent protein (GFP)-marked CD146+/CD31- cells indicated that they became CD31+ cells, which took part in EC structures with CD31+ wild-type ECs. EC network development depends on VEGF signaling, and VEGF and erythropoietin are expressed in the embryonic kidney even in the absence of any external hypoxic stimulus. Thus, the ex vivo embryonic kidney culture models adopted here provided novel ways for targeting renal EC development and demonstrated that CD146+ cells are critical for kidney vasculature development.

Original languageEnglish (US)
Pages (from-to)311-324
Number of pages14
JournalKidney international
Volume90
Issue number2
DOIs
StatePublished - Aug 1 2016

Keywords

  • endothelium
  • erythropoietin
  • glomerulus
  • kidney development
  • podocyte

ASJC Scopus subject areas

  • Nephrology

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