A coordinated progression of progenitor cell states initiates urinary tract development

Oraly Sanchez-Ferras,Mathieu Bourgey,Maxime Bouchard,Yu Chang Wang,Jiannis Ragoussis,Maria Sotiropoulou,Alain Pacis,Yuhong Zhang,Guillaume Bourque

doi:10.1038/s41467-021-22931-5

Oraly Sanchez-Ferras, Mathieu Bourgey + Show 7 more

Open Access

https://doi.org/10.1038/s41467-021-22931-5

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Abstract

The kidney and upper urinary tract develop through reciprocal interactions between the ureteric bud and the surrounding mesenchyme. Ureteric bud branching forms the arborized collecting duct system of the kidney, while ureteric tips promote nephron formation from dedicated progenitor cells. While nephron progenitor cells are relatively well characterized, the origin of ureteric bud progenitors has received little attention so far. It is well established that the ureteric bud is induced from the nephric duct, an epithelial duct derived from the intermediate mesoderm of the embryo. However, the cell state transitions underlying the progression from intermediate mesoderm to nephric duct and ureteric bud remain unknown. Here we show that nephric duct morphogenesis results from the coordinated organization of four major progenitor cell populations. Using single cell RNA-seq and Cluster RNA-seq, we show that these progenitors emerge in time and space according to a stereotypical pattern. We identify the transcription factors Tfap2a/b and Gata3 as critical coordinators of this progenitor cell progression. This study provides a better understanding of the cellular origin of the renal collecting duct system and associated urinary tract developmental diseases, which may inform guided differentiation of functional kidney tissue.

Highlights

The kidney and upper urinary tract develop through reciprocal interactions between the ureteric bud and the surrounding mesenchyme
The experiment yielded a total of 3396 cells, which clustered into 7 cell populations identified as nephric duct (ND), mesonephric tubules (MT), intermediate mesoderm, tailbud, hindgut, pharyngeal ectoderm and neural (Fig. 1b)
The collecting duct system of the kidney is generated by the ureteric bud (UB), which itself is derived from the formation of an epithelial duct (the ND)

Summary

Introduction

The kidney and upper urinary tract develop through reciprocal interactions between the ureteric bud and the surrounding mesenchyme. Ureteric bud branching forms the arborized collecting duct system of the kidney, while ureteric tips promote nephron formation from dedicated progenitor cells. It is well established that the ureteric bud is induced from the nephric duct, an epithelial duct derived from the intermediate mesoderm of the embryo. The cell state transitions underlying the progression from intermediate mesoderm to nephric duct and ureteric bud remain unknown. The UB is known to emerge from the nephric duct (ND), the central component of the pro/mesonephros (Fig. 1a) This primitive kidney starts with the formation of an epithelial duct (the ND) from intermediate mesoderm cells of mid-gestation embryos (embryonic day (E)8.75). We further define Gata[3] and Tfap2a/2b as critical regulators of the progenitor cell progression initiating urinary tract development

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Results

Conclusion