Direct Isolation and Characterization of Human Nephron Progenitors

Stem Cells Transl Med. 2017 Feb;6(2):419-433. doi: 10.5966/sctm.2015-0429. Epub 2016 Sep 9.


Mature nephrons originate from a small population of uninduced nephrogenic progenitor cells (NPs) within the cap mesenchyme. These cells are characterized by the coexpression of SIX2 and CITED1. Many studies on mouse models as well as on human pluripotent stem cells have advanced our knowledge of NPs, but very little is known about this population in humans, since it is exhausted before birth and strategies for its direct isolation are still limited. Here we report an efficient protocol for direct isolation of human NPs without genetic manipulation or stepwise induction procedures. With the use of RNA-labeling probes, we isolated SIX2+ CITED1+ cells from human fetal kidney for the first time. We confirmed their nephrogenic state by gene profiling and evaluated their nephrogenic capabilities in giving rise to mature renal cells. We also evaluated the ability to culture these cells without complete loss of SIX2 and CITED1 expression over time. In addition to defining the gene profile of human NPs, this in vitro system facilitates studies of human renal development and provides a novel tool for renal regeneration and bioengineering purposes. Stem Cells Translational Medicine 2017;6:419-433.

Keywords: Direct isolation of live cells; Human nephron progenitors; Smartflares.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Cell Separation / methods*
  • Cells, Cultured
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Mice
  • Morphogenesis
  • Nephrons / embryology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phenotype
  • Stem Cells / metabolism
  • Stem Cells / physiology*
  • Time Factors
  • Trans-Activators
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptome


  • Apoptosis Regulatory Proteins
  • CITED1 protein, human
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • SIX2 protein, human
  • Trans-Activators
  • Transcription Factors