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A coordinated progression of progenitor cell states initiates urinary tract development.

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.

SUBMITTER: Sanchez-Ferras O

PROVIDER: S-EPMC8113267 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTo support trials testing lifestyle interventions for lower urinary tract symptoms, often a consequence of benign prostatic hyperplasia, we estimated the incidence and progression rates of lower urinary tract symptoms in United States men unselected for benign prostatic hyperplasia.Materials and methodsWe studied men in the HPFS (Health Professionals Follow-Up Study) whom we asked to report periodically by mailed survey whether they had undergone surgery or used medications for lower urinary tract symptoms and to complete the International Prostate Symptom Score survey. For incidence we included 25,879 men with an International Prostate Symptom Score of 0 to 7 and no surgery history who were followed from 1992 to 2008. Incident moderate or worse lower urinary tract symptoms (6,058) were defined as an International Prostate Symptom Score of 15 or greater, surgery, or medication use. Modest or worse lower urinary tract symptoms were similarly defined but with an International Prostate Symptom Score of 8 or greater (11,352). For progression we included 9,628 men with an International Prostate Symptom Score of 8 to 14 and no surgery who were followed from when they first reported an International Prostate Symptom Score of 8 to 14 until 2008. Progression to severe lower urinary tract symptoms (2,557) was defined as an International Prostate Symptom Score of 20 or greater, surgery, or medication use. We estimated age specific and age standardized rates.ResultsIncidence and progression rates increased with age (p trend <0.0001), and progression rates were higher than incidence rates. The age standardized rates were incidence of moderate to worse lower urinary tract symptoms 18.5, incidence of modest or worse lower urinary tract symptoms 40.5 and progression to severe lower urinary tract symptoms 44.9 per 1,000 man-years.ConclusionsThe incidence and progression rates of lower urinary tract symptoms are high and increase steeply as men age. These rates may be used for planning adequately powered trials to test lifestyle interventions for lower urinary tract symptoms well before surgical or pharmacological treatment is indicated.

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A coordinated progression of progenitor cell states initiates urinary tract development.

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