Nephrons in the mammalian kidney are formed from self-renewing progenitors that reside within a niche defined by the cap mesenchyme and ureteric epithelial tip. As the mouse kidney develops, progenitor cells in the cap mesenchyme differentiate in response to inductive cues and exit the niche to form nephrons. This progenitor population is highly dynamic, migrating randomly and in response to niche cues, yet giving rise to nephrons in a coordinated, spatially defined manner.
We recently identified a subset of progenitors that express early markers of nephron commitment, yet migrate back into the progenitor population where they accumulate over time. Single cell RNA-seq and computational modelling suggest that these progenitors may traverse the transcriptional hierarchy between self-renewal and commitment in either direction. Commitment appears to be a stochastic process in which migration events dictate the duration of exposure to spatially defined cues.
We are now examining how these stochastic events are coordinated at the population-scale to enable subsets of migrating cells to aggregate and form epithelial nephrons. Using a modified explant imaging method we can capture migration data for entire niche neighbourhoods at sufficient resolution to follow individual progenitors over time. Matching this live cell data with high resolution 3D imaging of the same tissue allows us to correlate cell migration events with eventual cell fate. We are using this approach to examine how dynamic events within the niche contribute to robust organ patterning during development.