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Dev Cell. 2018 Jun 4;45(5):651-660.e4. doi: 10.1016/j.devcel.2018.05.010.

Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis.

Author information

1
Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
2
Molecular and Computational Biology, Division of Biological Sciences, University of Southern, Los Angeles, CA 90089, USA.
3
Maternal Fetal Medicine Division, University of Southern California, Los Angeles, CA, USA.
4
Molecular and Computational Biology, Division of Biological Sciences, University of Southern, Los Angeles, CA 90089, USA. Electronic address: andrewds@usc.edu.
5
Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: amcmahon@med.usc.edu.

Abstract

Mammalian nephrons arise from a limited nephron progenitor pool through a reiterative inductive process extending over days (mouse) or weeks (human) of kidney development. Here, we present evidence that human nephron patterning reflects a time-dependent process of recruitment of mesenchymal progenitors into an epithelial nephron precursor. Progressive recruitment predicted from high-resolution image analysis and three-dimensional reconstruction of human nephrogenesis was confirmed through direct visualization and cell fate analysis of mouse kidney organ cultures. Single-cell RNA sequencing of the human nephrogenic niche provided molecular insights into these early patterning processes and predicted developmental trajectories adopted by nephron progenitor cells in forming segment-specific domains of the human nephron. The temporal-recruitment model for nephron polarity and patterning suggested by direct analysis of human kidney development provides a framework for integrating signaling pathways driving mammalian nephrogenesis.

KEYWORDS:

fate; human; kidney; lineage; nephron; patterning; precursor; single-cell; time

PMID:
29870722
DOI:
10.1016/j.devcel.2018.05.010
[Indexed for MEDLINE]

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