• Nephron progenitors, the self-renewing cells that give rise to nephrons, are particularly metabolically active, relying primarily on glycolysis for energy generation early in development. (lww.com)
  • As development progresses, nephron progenitors switch from glycolysis to mitochondrial respiration for energy-mediated by an unknown mechanism-and undergo differentiation. (lww.com)
  • In addition to identifying VHL as a critical regulator of nephron progenitors' metabolic switching, the authors' findings demonstrate that this switch also plays a large role in the differentiation process, and suggest that VHL is required for normal kidney development. (lww.com)
  • Nephron progenitors, the cell population that give rise to the functional unit of the kidney, are metabolically active and self-renew under glycolytic conditions. (lww.com)
  • To explore VHL as a regulator defining nephron progenitor self-renewal versus differentiation, we bred Six2-TGC tg mice with VHL lox/lox mice to generate mice with a conditional deletion of VHL from Six2 + nephron progenitors. (lww.com)
  • By embryonic day 15.5, kidneys of nephron progenitor cell-specific VHL knockout mice begin to exhibit reduced maturation of nephron progenitors. (lww.com)
  • VHL knockout nephron progenitors also exhibit persistent Six2 and Wt1 expression, as well as decreased mitochondrial respiration and prolonged reliance on glycolysis. (lww.com)
  • These renal vesicles connect the collecting duct and ureter, developing into metanephric nephron progenitors ( Fig. 1 ) [ 8 , 9 ]. (j-organoid.org)
  • In mammals, the nephron consists of the renal glomerulus inside Bowman's capsule, the proximal convoluted tubule, the proximal straight tubule, the loop of Henle, and the distal convoluted tubule. (wikipedia.org)
  • There is a blood-filtering part of the nephron in the cortex - the renal corpuscle, from which the renal tubule extends to the medulla into the loop of Henle, then the tubule returns back to the cortex and with its distal end flows into its collecting duct that is common to several nephrons. (wikipedia.org)
  • Calcium reabsorption in the distal nephron of the kidney is functionally coupled to sodium transport. (bvsalud.org)
  • Recent work suggested that CaSR signals via the WNK-SPAK/OSR1 cascade to modulate salt reabsorption along the distal nephron. (bvsalud.org)
  • Later, during nephron segmentation, expression becomes restricted to the intermediate tubule region of the proximal-distal axis. (silverchair.com)
  • At the tailbud stage (stage 25-30),differentiation of the three basic segments occurs: the corpuscle, the tubules and the duct. (silverchair.com)
  • Our findings identify a novel role for VHL in mediating nephron progenitor differentiation through metabolic regulation, and suggest that VHL is required for normal kidney development. (lww.com)
  • In contrast to earlier models that featured nephron-like structures, these advances have improved the differentiation efficiency and similarity to the human kidney. (j-organoid.org)
  • Using the transporter profiling approach, Dr. McDonough and her colleagues have defined how stimuli such as dietary salts, Ang II, kidney injury, and immune cytokines increase renal sodium transport in a region specific manner along the nephron and how resultant hypertension provokes intrarenal responses to decrease sodium reabsorption (via pressure natriuresis), a response that defines the blood pressure set point in the kidney. (usc.edu)
  • One functional component of the kidney, the nephron, carries out tasks such as filtration and reabsorption. (j-organoid.org)
  • Reabsorption of glucose predominantly occurs on the brush border membrane of the convoluted segment of the proximal tubule. (medscape.com)
  • The cortex and medulla are based on nephrons together with an extensive network of blood vessels and capillaries, as well as collecting ducts, into which nephrons empty, and renal interstitium. (wikipedia.org)
  • Here, we have compiled gene lists of the acetyltransferases and deacetylases in the mammalian genomes and mapped their mRNA expression along the renal tubule. (bvsalud.org)
  • Renal complexity is characterized by several functionally and structurally distinct segments. (j-organoid.org)
  • The interstitial stroma, another subcompartment of the metanephric nephron, is characterized by the expression of the transcription factor forkhead box D1 ( Foxd1 ). (j-organoid.org)
  • Our project focuses on characterizing and optimizing this approach to improve tubular maturation and cellular function and generating reporter lines for the isolation of specific cell types. (atlas-d2k.org)
  • To study the potential role in this metabolic shift of von Hippel-Lindau (VHL), a protein component of a ubiquitin ligase complex, the authors generated nephron progenitor cell-specific VHL knockout mice. (lww.com)
  • Here we show that hPSC-KCs self-organize into kidney organoids that functionally recapitulate tissue-specific epithelial physiology, including disease phenotypes after genome editing. (nature.com)
  • GSK3β inhibition differentiates spheroids into segmented, nephron-like kidney organoids containing cell populations with characteristics of proximal tubules, podocytes and endothelium. (nature.com)
  • Presently, kidney organoids contain not only nephrons and ureteric buds but also stromal cells. (j-organoid.org)
  • There is a blood-filtering part of the nephron in the cortex - the renal corpuscle, from which the renal tubule extends to the medulla into the loop of Henle, then the tubule returns back to the cortex and with its distal end flows into its collecting duct that is common to several nephrons. (wikipedia.org)
  • Here, we used RNA-seq coupled with classic renal tubule microdissection to comprehensively profile gene expression in each of 14 renal tubule segments from the proximal tubule through the inner medullary collecting duct of rat kidneys. (nih.gov)
  • Cellular interactions among nephron, interstitial, and collecting duct progenitors drive mammalian kidney development. (atlas-d2k.org)
  • These renal vesicles connect the collecting duct and ureter, developing into metanephric nephron progenitors ( Fig. 1 ) [ 8 , 9 ]. (j-organoid.org)
  • All of these functional phenotypes are distinct from effects in epiblast spheroids, indicating that they are tissue specific. (nature.com)
  • THE RVs are the precursors to functional nephrons, as they twist and elongate into tightly patterned and segmented tubules (forming comma-shaped and S-shaped intermediary bodies) that remain fused with the ureteric branches to form contiguous tubules with the collecting ducts. (mechanobio.info)
  • The functional unit of the mammalian kidney is the nephron. (atlas-d2k.org)
  • An understanding of the diversity of nephron cell types is essential for the goals of (Re)Building A Kidney Consortium where generating functional kidney structures is the consortium target. (atlas-d2k.org)
  • These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species. (atlas-d2k.org)
  • One of the main reasons is that mammals can partly repair their nephrons (the functional units of the kidney), but cannot regenerate new ones. (elifesciences.org)
  • Populations of highly proliferative, multipotent cells of renal origin show the ability to engraft in injured kidneys, mitigate functional loss and occasionally show the ability to generate nephrons de novo . (biomedcentral.com)
  • One functional component of the kidney, the nephron, carries out tasks such as filtration and reabsorption. (j-organoid.org)
  • In mice, Six2+ nephron progenitor cells (NPCs) and Foxd1+ interstitial progenitor cells (IPCs) form largely distinct lineage compartments at the onset of metanephric kidney development. (atlas-d2k.org)
  • The interstitial stroma, another subcompartment of the metanephric nephron, is characterized by the expression of the transcription factor forkhead box D1 ( Foxd1 ). (j-organoid.org)
  • Because of this, we will discuss potential stem cell sources based on anatomical origin, namely from the Bowman's capsule, the renal papilla and the nephron tubules. (biomedcentral.com)
  • The mammalian kidneys are the paired organ of the urinary system of mammals, which is a type of metanephric kidney. (wikipedia.org)
  • The mammalian nephric system is one of the most complex organ systems to be formed during embryogenesis and involves the interdependent development of two major components: the ureteric bud and the metanephric mesenchyme. (mechanobio.info)
  • The rapid, recent appearance of comprehensive unbiased gene expression data in the various renal tubule segments, chiefly RNA sequencing and protein mass spectrometry data, has provided a means of identifying patterns of GPCR expression along the renal tubule. (nih.gov)
  • Cysts develop from renal tubule segments and most detach from the parent tubule after they grow to a few millimeters in size. (medscape.com)
  • As in mice, each progenitor population adopts a stereotypical arrangement in the human nephron-forming niche: NPCs capped outgrowing ureteric branch tips, whereas IPCs were sandwiched between the NPCs and the renal capsule. (atlas-d2k.org)
  • There is a significant need for genetically diverse cell culture platforms that accurately reconstitute tissue-specific epithelial function, particularly in humans where species-specific toxicology and disease pathophysiology is of significant biomedical relevance. (nature.com)
  • Podocytes are a specialized type of epithelial cell that encase the glomerular capillaries with interdigitated foot processes to regulate filtration into the nephron [ 8 ]. (biomedcentral.com)
  • During nephron regeneration, the formation of nephrons is supported by RICs that form a network to wrap the RPC aggregates. (elifesciences.org)
  • Overall, these findings indicate that RICs provide a necessary microenvironment for rapid nephrogenesis during nephron regeneration. (elifesciences.org)
  • The field has aquired a good general base of knowledge, but scrutiny of the techniques and outcomes will be necessary to move toward a unified explanation of renal regeneration and the role of organ-specific stem cells in the kidney. (biomedcentral.com)
  • Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. (atlas-d2k.org)
  • Finally, the sexual differentiation of many structures passes from an indifferent stage, in which male and female differences are not readily apparent, to a male or female pathway, depending on the presence of specific promoting or inhibiting factors acting on the structure. (clinicalgate.com)
  • Renal complexity is characterized by several functionally and structurally distinct segments. (j-organoid.org)
  • The function of each renal tubule segment depends on the genes expressed therein. (nih.gov)
  • as an example, mutations in genes producing podocyte specific gene products result in glomerular nephritis. (atlas-d2k.org)
  • Whether the hPSC-KCs can reconstitute tissue-specific phenotypes is currently unknown. (nature.com)
  • The cortex and medulla are based on nephrons together with an extensive network of blood vessels and capillaries, as well as collecting ducts, into which nephrons empty, and renal interstitium. (wikipedia.org)