[PDF][PDF] Progressive recruitment of mesenchymal progenitors reveals a time-dependent process of cell fate acquisition in mouse and human nephrogenesis

NO Lindström, GDS Brandine, T Tran, A Ransick… - Developmental cell, 2018 - cell.com
NO Lindström, GDS Brandine, T Tran, A Ransick, G Suh, J Guo, AD Kim, RK Parvez…
Developmental cell, 2018cell.com
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 …
Summary
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.
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