Aberrant centrosome biogenesis disrupts nephron and collecting duct progenitor growth and fate resulting in fibrocystic kidney disease
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PROVIDER: PRJNA1050195 | ENA |
REPOSITORIES: ENA
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Project description:Mutations that disrupt centrosome biogenesis or function cause congenital kidney developmental defects and fibrocystic pathologies. Yet, how centrosome dysfunction results in the kidney disease phenotypes remains unknown. Here, we examined the consequences of conditional knockout of the ciliopathy gene Cep120, essential for centrosome duplication, in the nephron and collecting duct progenitor niches of the mouse embryonic kidney. Cep120 loss led to reduced abundance of both cap mesenchyme and ureteric bud populations, due to a combination of delayed mitosis, increased apoptosis, and premature differentiation of progenitor cells. These defects resulted in dysplastic kidneys at birth, which rapidly formed cysts, displayed increased interstitial fibrosis, and decline in kidney function. RNA sequencing of embryonic and postnatal kidneys from Cep120-null mice identified changes in pathways essential for development, fibrosis, and cystogenesis. Our study defines the cellular and developmental defects caused by centrosome dysfunction during kidney morphogenesis, and identifies new therapeutic targets for patients with renal centrosomopathies.
2023-12-08 | GSE249693 | GEO
Project description:Mutations that disrupt centrosome biogenesis or function cause congenital kidney developmental defects and fibrocystic pathologies. Yet, how centrosome dysfunction results in the kidney disease phenotypes remains unknown. Here, we examined the consequences of conditional knockout of the ciliopathy gene Cep120, essential for centrosome duplication, in the nephron and collecting duct progenitor niches of the mouse embryonic kidney. Cep120 loss led to reduced abundance of both cap mesenchyme and ureteric bud populations, due to a combination of delayed mitosis, increased apoptosis, and premature differentiation of progenitor cells. These defects resulted in dysplastic kidneys at birth, which rapidly formed cysts, displayed increased interstitial fibrosis, and decline in kidney function. RNA sequencing of embryonic and postnatal kidneys from Cep120-null mice identified changes in pathways essential for development, fibrosis, and cystogenesis. Our study defines the cellular and developmental defects caused by centrosome dysfunction during kidney morphogenesis, and identifies new therapeutic targets for patients with renal centrosomopathies.
2023-12-08 | GSE249692 | GEO
Project description:Mutations that disrupt centrosome biogenesis or function cause congenital kidney developmental defects and fibrocystic pathologies. Yet, how centrosome dysfunction results in the kidney disease phenotypes remains unknown. Here, we examined the consequences of conditional knockout of the ciliopathy gene Cep120, essential for centrosome duplication, in the nephron and collecting duct progenitor niches of the mouse embryonic kidney. Cep120 loss led to reduced abundance of both cap mesenchyme and ureteric bud populations, due to a combination of delayed mitosis, increased apoptosis, and premature differentiation of progenitor cells. These defects resulted in dysplastic kidneys at birth, which rapidly formed cysts, displayed increased interstitial fibrosis, and decline in kidney function. RNA sequencing of embryonic and postnatal kidneys from Cep120-null mice identified changes in pathways essential for development, fibrosis, and cystogenesis. Our study defines the cellular and developmental defects caused by centrosome dysfunction during kidney morphogenesis, and identifies new therapeutic targets for patients with renal centrosomopathies.
2023-12-08 | GSE249689 | GEO
Project description:Aberrant centrosome biogenesis disrupts nephron and collecting duct progenitor growth and fate resulting in fibrocystic kidney disease [P15]
| PRJNA1050199 | ENA
Project description:Aberrant centrosome biogenesis disrupts nephron and collecting duct progenitor growth and fate resulting in fibrocystic kidney disease [Embryonic]
| PRJNA1050200 | ENA
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: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, alphaENaC). 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. Keywords: time course
2009-10-22 | GSE17739 | GEO
Project description:Aldosterone is arguably the single most important hormone implicated in the control of blood pressure and extracellular fluid volume in mammals. It acts primarily by increasing the rate of transepithelial sodium transport in the kidney tubules. Several monogenetic defects resulting in hypertension have now been attributed to abnormalities in sodium handling within the aldosterone-sensitive distal nephron, where the epithelial sodium channel, ENaC, constitutes the rate-limiting step of sodium transport. To date, the transcription-dependent aldosterone-signaling pathway between receptor and membrane transport effectors, remains incompletely understood. The broad aim of our study is to explore these intracellular signaling pathways that are critical to the functioning of sodium channels. Microarray analysis in an aldosterone-responsive kidney cortical collecting duct cell line (mpkCCDc14), allowed us to identify many potential aldosterone-regulated transcripts. The present study describes the identification, and possible physiological relevance of various aldosterone-regulated transcripts. The results of this study promise to extend our understanding of the molecular basis of aldosterone-regulated sodium transport in kidney epithelia, and provide approaches for regulating this process in disease states such as congestive heart failure and hypertension. Keywords: hormone effect
2005-07-15 | GSE2933 | GEO
Project description:Transcriptional profiling of new born mouse kidney collecting duct (CD) cells comparing the infuence of gestational high salt stress on gene expression remolding of BdkrB2 receptor knockout CD cells with that of BdkrB2 receptor wild type CD cells. The BdkrB2 receptor has been shown to be playing a role in renal vascular tone, kidney secretion and reabsorption function, normal kidney development, while impaired BdkrB2 receptor in kidney shown being associated with renal agenesis and renal dysplasia. Goal was to determine the effects of BdkrB2 receptor knockout together with gestational high salt stress on collecting duct gene expression pattern.
2013-08-08 | GSE49616 | GEO
Project description:Here, establishing expansion cultures of hiPSC-derived ureteric bud tip cells, an embryonic precursor that gives rise to collecting ducts, we succeeded in advancing the developmental stage of collecting duct organoids and showed that all collecting duct organoids derived from PKD1-/- hiPSCs spontaneously develop multiple cysts, clarifying the initiation mechanisms of cystogenesis.
2023-11-30 | GSE215875 | GEO