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

• DOI: 10.1016/j.devcel.2018.05.010
• Publication Date: 2018-06-04T14:39:15Z
• Authors: Nils O. Lindström; Guilherme De Sena...; Tracy Tran; Andrew Ransick; Gio Suh; Jinjin Guo; Albert D. Kim; Riana K. Parvez; Seth W. Ruffins; Elisabeth A. Rutl...; Matthew E. Thornton; Brendan Grubbs; Jill A. McMahon; Andrew D. Smith; Andrew P. McMahon
• Keywords: Progenitor

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.