Rhythmic nephron formation in the developing kidney [E18_stroma_bulkRNAseq]

The mammalian kidney achieves massive parallelization of function by exponentially duplicating nephron-forming niches during development. Each niche caps a tip of the ureteric bud epithelium (the future urinary collecting duct tree) as it undergoes branching morphogenesis, while nephron progenitors within niches balance self-renewal and differentiation to early nephron cells. Nephron formation rate approximately matches branching rate over a large fraction of mouse gestation, yet the nature of this apparent pace-maker is unknown. Here we correlate spatial transcriptomics data with branching 'life-cycle' to discover rhythmically alternating signatures of nephron progenitor differentiation and renewal across Wnt, Hippo/Yap, retinoic acid (RA), and other pathways. Our data bring temporal resolution to the renewal vs. differentiation balance in the nephrogenic niche and inform new strategies to achieve self-sustaining nephron formation in synthetic human kidney tissues. Overall design: RNA-seq of nephrogenic stroma isolated from pooled E18 wild-type CD1 mouse kidneys. Conditions include stroma subject to 18 hours of culture on PDMS substrates incubated in low or high concentration fibronectin solutions to promote low or high adhesion, respectively. Samples include low and high adhesion conditions from 3 litter-matched replicates.