Abstract
Progenitor self-renewal and differentiation is often regulated by spatially restricted cues within a tissue microenvironment. Here, we examine how progenitor cell migration impacts regionally induced commitment within the nephrogenic niche in mice. We identify a subset of cells that express Wnt4, an early marker of nephron commitment, but migrate back into the progenitor population where they accumulate over time. Single cell RNA-seq and computational modelling of returning cells reveals that nephron progenitors can traverse the transcriptional hierarchy between self-renewal and commitment in either direction. This plasticity may enable robust regulation of nephrogenesis as niches remodel and grow during organogenesis.
Highlights
Mammalian kidney morphogenesis is propagated by reciprocal signalling between progenitor cell populations at the periphery of the developing kidney (Combes et al, 2015; Costantini and Kopan, 2010; Kopan et al, 2014; Little and McMahon, 2012)
Nephron progenitor cells play a central role in this process, signalling to the tips of the ureteric epithelium to promote branching morphogenesis, and providing a pool of cells from which nephron formation can be induced (Combes et al, 2015; Costantini and Kopan, 2010; Kobayashi et al, 2008)
GFP signal was not observed within nephron progenitor cells on top of the tip
Summary
Mammalian kidney morphogenesis is propagated by reciprocal signalling between progenitor cell populations at the periphery of the developing kidney (Combes et al, 2015; Costantini and Kopan, 2010; Kopan et al, 2014; Little and McMahon, 2012). Much progress has recently been made in understanding the signals that regulate nephron progenitor fate (Brown et al, 2013; Brown et al, 2015; Combes et al, 2015; Li et al, 2016; Park et al, 2012; Park et al, 2007). Nephron progenitor cells surround the tips of the ureteric epithelium forming a ‘cap mesenchyme’ domain that is embedded within, but distinct from cortical stroma and vasculature. Together these populations form the nephrogenic niche, with the least committed nephron progenitor cells at the ‘top’ of the tip and nephron formation occurring at the ‘bottom’, in the junction between tip and stalk of the ureteric epithelium (Mugford et al, 2009)
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