Single-Cell Spatial Mapping of Human Kidney Development Reveals Cellular Niches and Lineage Dynamics

Among these, we highlight the role of WNT, FGF, and RET signaling, which have been classically described in mouse nephrogenesis but are now observed in human kidney development. In examining ligand expression, we estimate and quantify the microenvironment for each cell, enabling us to identify ligands associated with driving differentiation trajectories, and identify microenvironments which predict gene expression within cell types and differentiation status.

Using this approach, we identified IGF2-mediated signaling as enriched within the blastema and associated with renewal signals suggesting its role as a niche renewal factor. This finding may explain the alterations in nephrogenesis associated with uncontrolled maternal diabetes, providing new insights how the local cellular environment shapes cellular differentiation in the kidney and potential therapeutic interventions.