Single cell profiling reveals sex, lineage and regional diversity in adult mouse kidney
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE129798 | GEO | 2019/11/04
REPOSITORIES: GEO
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Project description:The kidney is a complex organ composed of more than 30 terminally differentiated cell types that all are required to perform its numerous homeostatic functions. De-fects in kidney development are a significant cause of chronic kidney disease in children, which can lead to kidney failure that can only be treated by transplant or dialysis. A better understanding of molecular mechanisms that drive kidney development is important for designing strategies to enhance renal repair and regeneration. In this study, we profiled gene expression in the developing mouse kidney at embryonic day 14.5 at single cell resolution. Consistent with previous studies, clusters with distinct transcriptional signatures clearly identify major compartments and cell types of the developing kidney. Cell cycle activity distinguishes between the “primed” and “self-renewing” sub-populations of nephron progenitors, with increased expression of the cell cycle related genes Birc5, Cdca3, Smc2 and Smc4 in “primed” nephron progenitors. Augmented Birc5 expression was also detected in immature distal tubules and a sub-set of ureteric bud cells, suggesting that Birc5 might be a novel key molecule required for early events of nephron patterning and tubular fusion between the distal nephron and the collecting duct epithelia.
2021-11-24 | GSE158166 | GEO
Project description:miRNA plays a role as post-transcriptional regulator. However, miRNAs in the kidney collecting duct cell have not been well understood. So we aimed to profile miRNAs in the kidney inner medullary collecting duct (IMCD) cells, and to identify the vasopressin-responsive miRNAs in the kidney IMCD cells. The microarray assay revealed that relative expression of miRNAs in the kidney IMCD cells was changed by desmopressin (dDAVP) stimulation. Fresh IMCD tubules were prepared from rat kidney and incubated in the medium in the absence or presence of dDAVP (1 nM, 2 h). Total RNA purified from IMCD tubules was used to analyze miRNA expression by GeneChipM-BM-. miRNA 3.0 Array (Affymetrix).
2014-06-21 | E-GEOD-58693 | biostudies-arrayexpress
Project description:Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e. distal convoluted tubule (DCT) and connecting tubule (CNT) and, the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, M-oM-^AM-!ENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function. Experiment Overall Design: We examined the temporal profiles of gene expression in mouse distal nephron segments and collecting ducts. The RNA was extracted from microdissected distal convoluted tubules and connecting tubules (DCT/CNT samples) or, cortical collecting ducts (CCD samples). Animals were sacrificed for microdissection every 4 hours, i.e. at ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20 (ZT M-bM-^@M-^S Zeitgeber (circadian) time, indicates time of light-on as ZT0 and time of light-off as ZT12). The microarray hybridization was performed in duplicates on two pools of RNA composed of equivalent amounts of RNA prepared from five animals at each ZT time-point.
2009-10-30 | E-GEOD-17739 | biostudies-arrayexpress
Project description:Our laboratory's interest is in understanding the molecular principles that underlie the regional organization of the mammalian metanephric kidney. Our goal is to generate a detailed spatial map of the cellular expression of selected regulatory genes during mammalian kidney development. The goal of this study is to identify genes expressed during the morphogenesis of the nephron. By profiling two specific developmental nephron structures, we expect to identify genes expressed in both, and unique to each, which suggests they may play a role in the underlying mechanism responsible for the morphogenesis. Experiment Overall Design: Two early nephron structures, the renal vesicle and the s-shaped body, and the collecting duct system, were microdissected from E14.5 kidneys based on morphological criteria. Antibody and lectin staining together with RT-PCR were used for identity verification and for exclusion of contamination by other tissues. Samples are minimally pooled for amplification. A biological replicate is a single minimally pooled sample. RNA isolated from the collected structures was put through two rounds of T7-driven amplification to obtain the microgram quantities of cRNA needed for hybridization to Affymetrix microarrays. Detection of genes previously shown to be expressed in these early structures, such as Wt1, Wnt4 and Pax8, validates the data from the screen. The collecting duct sample serves as a reference sample for comparing the renal vesicle and s-shaped body comparison in this study.
2008-06-14 | E-GEOD-6287 | biostudies-arrayexpress
Project description:Recent studies using human pluripotent stem cells (hPSCs) have developed protocols to induce kidney-lineage cells and reconstruct kidney organoids. However, the separate generation of metanephric nephron progenitors (NPs), mesonephric NPs and ureteric bud (UB) cells, which constitute embryonic kidneys, in in vitro differentiation culture systems has not been fully investigated. Here we created a culture system in which these mesoderm-like cell types as well as paraxial and lateral plate mesoderm-like cells were separately generated from hPSCs. We succeeded in recapitulating nephrogenic niches from separately induced metanephric NP-like and UB-like cells, which were subsequently differentiated into glomeruli, renal tubules and collecting ducts in vitro and further vascularized in vivo. Our selective differentiation protocols should contribute to understanding the mechanisms underlying human kidney development and diseases and also supply cell sources for regenerative therapies.
2020-07-15 | GSE146118 | GEO
Project description:Recent studies using human pluripotent stem cells (hPSCs) have developed protocols to induce kidney-lineage cells and reconstruct kidney organoids. However, the separate generation of metanephric nephron progenitors (NPs), mesonephric NPs and ureteric bud (UB) cells, which constitute embryonic kidneys, in in vitro differentiation culture systems has not been fully investigated. Here we created a culture system in which these mesoderm-like cell types as well as paraxial and lateral plate mesoderm-like cells were separately generated from hPSCs. We succeeded in recapitulating nephrogenic niches from separately induced metanephric NP-like and UB-like cells, which were subsequently differentiated into glomeruli, renal tubules and collecting ducts in vitro and further vascularized in vivo. Our selective differentiation protocols should contribute to understanding the mechanisms underlying human kidney development and diseases and also supply cell sources for regenerative therapies.
2020-07-15 | GSE146117 | GEO
Project description:Our laboratory's interest is in understanding the molecular principles that underlie the regional organization of the mammalian metanephric kidney. Our goal is to generate a detailed spatial map of the cellular expression of selected regulatory genes during mammalian kidney development. The goal of this study is to identify genes expressed during the morphogenesis of the nephron. By profiling two specific developmental nephron structures, we expect to identify genes expressed in both, and unique to each, which suggests they may play a role in the underlying mechanism responsible for the morphogenesis. Experiment Overall Design: Two early nephron structures, the renal vesicle and the s-shaped body, and the collecting duct system, were microdissected from E14.5 kidneys based on morphological criteria. Antibody and lectin staining together with RT-PCR were used for identity verification and for exclusion of contamination by other tissues. Samples are minimally pooled for amplification. A biological replicate is a single minimally pooled sample. RNA isolated from the collected structures was put through two rounds of T7-driven amplification to obtain the microgram quantities of cRNA needed for hybridization to Affymetrix microarrays. Detection of genes previously shown to be expressed in these early structures, such as Wt1, Wnt4 and Pax8, validates the data from the screen. The collecting duct sample serves as a reference sample for comparing the renal vesicle and s-shaped body comparison in this study. We also tested amplification of single s-shaped bodies as compared to pooled samples and found the minimally pooled samples resulted in better data for this study (better sensitivity when inspected for genes known to be expressed in s-shaped bodies).
2008-06-14 | E-GEOD-6309 | biostudies-arrayexpress
Project description:We used micro-dissection techniques and/or FACS to isolate cell types from the developing and adult kidney (E11.5 ureteric buds, E12.5, P1 and P4 cap mesenchyme, E15.5 collecting ducts, proximal tubules, ureter, Adult renal proximal tubules, podocytes, endothelial and mesangial cells). RNA-SEQ analysis was performed to determine the transcriptional profile of each cell type, identify component specific transcripts and isoforms and cell-type specific long-noncoding RNAs. In addition the unbiased nature of RNA-SEQ will potentially identify novel transcripts that have not been annotated in the database. Total RNA is obtained from micro-dissected and/or FACS isolated embryonic and adult kidney components. The long term goal is to generate a transcriptional atlas of developing kidney.
2015-01-27 | E-GEOD-64959 | biostudies-arrayexpress
Project description:During development, distinct progenitors contribute to the nephrons versus the ureteric epithelium of the kidney. Indeed, previous pluripotent stem cell-derived models of kidney tissue either contain nephrons or pattern specifically to the ureteric epithelium. By reanalysing the transcriptional distinction between distal nephron and ureteric epithelium in human fetal kidney, we show here that while existing nephron-containing kidney organoids contain distal nephron epithelium and no ureteric epithelium, this distal nephron segment alone displays significant in vitro plasticity and can adopt a ureteric epithelial tip identity when isolated and cultured in defined conditions. “Induced” ureteric epithelium cultures can be cryopreserved, serially passaged without loss of identity and transitioned towards a collecting duct fate. Indeed, cultures harbouring loss-of-function mutations in PKHD1 recapitulate the cystic phenotype associated with autosomal recessive polycystic kidney disease.
2021-01-15 | GSE161255 | GEO
Project description:The nephron, functional unit of the vertebrate kidney, is specialized in metabolic wastes excretion and body fluids osmoregulation. Given the high evolutionary conservation of gene expression and segmentation patterning between mammalian and amphibian nephrons, the Xenopus laevis pronephric kidney offers a simplified model for studying nephrogenesis. The Lhx1 transcription factor plays critical roles in kidney development, regulating target gene expression by forming multiprotein complexes with LIM binding protein 1 (Ldb1). However, few Lhx1-Ldb1 cofactors have been identified for this organ formation. By tandem- affinity purification from kidney-induced Xenopus animal caps, we identified single-stranded DNA binding protein 2 (Ssbp2) to interact with the Ldb1-Lhx1 complex. Ssbp2 is expressed in the Xenopus pronephros, and knockdown prevents normal morphogenesis and differentiation of the glomus and the convoluted renal tubules. We demonstrate a role for a member of the Ssbp family in kidney organogenesis and provide evidence of a fundamental function for the Ldb1-Lhx1-Ssbp transcriptional complexes in embryonic development.
2023-10-24 | PXD041761 | Pride