The current understanding of mammalian kidney development is largely based on mouse models. Recent landmark studies revealed pervasive differences in renal embryogenesis between mouse and human. The scarcity of detailed gene expression data in humans therefore hampers a thorough understanding of human kidney development and the possible developmental origin of kidney diseases. In this paper, we present a single-cell transcriptomics study of the human fetal kidney. We identified 22 cell types and a host of marker genes. Comparison of samples from different developmental ages revealed continuous gene expression changes in podocytes. To demonstrate the usefulness of our data set, we explored the heterogeneity of the nephrogenic niche, localized podocyte precursors, and confirmed disease-associated marker genes. With close to 18,000 renal cells from five different developmental ages, this study provides a rich resource for the elucidation of human kidney development, easily accessible through an interactive web application.

Single-cell analysis provides insights into cellular heterogeneity and dynamics of individual cells. This Feature highlights recent developments in key analytical techniques suited for single-cell metabolic analysis with a special focus on mass spectrometry-based analytical platforms and RNA-seq as well as imaging techniques that reveal stochasticity in metabolism.

Glomerulonephritis is characterized by the proliferation and apoptosis of mesangial cells (MC). The parathyroid-hormone related protein (PTHrP) is a locally active cytokine that affects these phenomena in many cell types, through either paracrine or intracrine pathways. The aim of this study was to evaluate the effect of both PTHrP pathways on MC proliferation and apoptosis. In vitro studies were based on MC from male transgenic mice allowing PTHrP-gene excision by a CreLoxP system. MC were also transfected with different PTHrP constructs: wild type PTHrP, PTHrP devoid of its signal peptide, or of its nuclear localization sequence. The results showed that PTHrP deletion in MC reduced their proliferation even in the presence of serum and increased their apoptosis when serum-deprived. PTH1R activation by PTHrP(1-36) or PTH(1-34) had no effect on proliferation but improved MC survival. Transfection of MC with PTHrP devoid of its signal peptide significantly increased their proliferation and minimally reduced their apoptosis. Overexpression of PTHrP devoid of its nuclear localization sequence protected cells from apoptosis without changing their proliferation. Wild type PTHrP transfection conferred both mitogenic and survival effects, which seem independent of midregion and C-terminal PTHrP fragments. PTHrP-induced MC proliferation was associated with p27(Kip1) down-regulation and c-Myc/E2F1 up-regulation. PTHrP increased MC survival through the activation of cAMP/protein kinase A and PI3-K/Akt pathways. These results reveal that PTHrP is a cytokine of multiple roles in MC, acting as a mitogenic factor only through an intracrine pathway, and reducing apoptosis mainly through the paracrine pathway. Thus, PTHrP appears as a probable actor in MC injuries.

Effects of pesticides on mesenchymal stem cell : mesenchymal stem cells, pesticides, pesticide mixture, senescence, tumorigenesis, CO and FMV developed the concepts and designed the experiments; MH performed in vitro experiments with the help of LO; CP and MH performed the SeaHorse experiments and analyses. VT, PA, JD, RB and JA performed in vivo experiments and analyses. DH and PN help to design in vivo experiments and to discuss results. MH, CO and FMV wrote the paper; all authors analysed results, wrote the methods section and edited the manuscript 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 (Viviers, Belgium). The references of the antibodies used in this study are listed in Table S1. that we used as a positive control. rapidly eliminated (in whole or in part) by the body. We considered the case of a total 92 absorption of this ingested amount and then its dilution in 5 liters of blood in a subject of 60 93Kg, in order to obtain the blood concentration (mg/l) to which the various organs could be 94 theoretically exposed. Finally, from the molar mass of each pesticide, we calculated a 95 concentration in µmole/L. 96Pesticides were dissolved in DMSO and mixtures were prepared at the three aforementioned 97 doses. Whatever the dose applied, the maximal volumes of DMSO ± pesticides added to the 98 media did not exceed 1/1000 (v/v) of the medium. Throughout the study, cells were treated 99 with pesticides mixture for 21 days and media were changed every three days.