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Controlling proximal nephron precursor differentiation to generate proximal-biased kidney organoids with emerging maturity [snRNA-Seq]

ABSTRACT: Controlling proximal nephron precursor differentiation to generate proximal-biased kidney organoids with emerging maturity [snRNA-Seq]

PROVIDER: PRJNA1231013 | ENA |

REPOSITORIES: ENA

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Controlling proximal nephron precursor differentiation to generate proximal-biased kidney organoids with emerging maturity [scRNA-Seq]

Project description:Controlling proximal nephron precursor differentiation to generate proximal-biased kidney organoids with emerging maturity [scRNA-Seq]

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Controlling proximal nephron precursor differentiation to generate proximal-biased kidney organoids with emerging maturity [snRNA-Seq]

Project description:The kidney maintains fluid homeostasis by reabsorbing essential compounds and excreting waste. Proximal tubule cells, crucial for reabsorbing sugars, ions, and amino acids, are highly susceptible to injury, often leading to pathologies necessitating dialysis or transplants. Human pluripotent stem cell-derived kidney organoids offer a platform to model renal development, function, and disease, but proximal nephron differentiation and maturation in these structures is incomplete. Here, we drive proximal tubule development in pluripotent stem cell-derived kidney organoids by mimicking in vivo proximal differentiation. Transient PI3K inhibition during early nephrogenesis activates Notch signaling, shifting nephron axial differentiation towards epithelial and proximal precursor states that mature to proximal convoluted tubule cells broadly expressing physiology-imparting solute carriers including organic cation and organic anion family members. The “proximal-biased” organoids thus acquire function, and on exposure to nephrotoxic injury, display tubular collapse and DNA damage, and upregulate injury response markers HAVCR1/KIM1 and SOX9 while downregulating proximal transcription factor HNF4A. Here, we show that proximally biased human-derived kidney organoids provide a robust model to study nephron development, injury responses, and a platform for therapeutic discovery.

2025-08-03 | GSE290931 | GEO

Controlling proximal nephron precursor differentiation to generate proximal-biased kidney organoids with emerging maturity [scRNA-Seq]

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Controlling proximal nephron precursor differentiation to generate proximal-biased kidney organoids with emerging maturity [bulk RNA-seq]

Project description:Controlling proximal nephron precursor differentiation to generate proximal-biased kidney organoids with emerging maturity [bulk RNA-seq]

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Controlling proximal nephron precursor differentiation to generate proximal-biased kidney organoids with emerging maturity [bulk RNA-seq]

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Proximal and Distal Nephron-specific Adaptation to Furosemide

Project description:Proximal and Distal Nephron-specific Adaptation to Furosemide

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Revisiting the Role of Notch in Nephron Segmentation Confirms A Role for Proximal Fate Selection During Mouse and Human Nephrogenesis

Project description:Notch signaling promotes maturation of nephron epithelia, but its proposed contribution to nephron segmentation into proximal and distal domains has been called into doubt. We leveraged single cell and bulk RNA-seq, quantitative immunofluorescent lineage/fate tracing, and genetically modified human iPSC to revisit this question in developing mouse kidneys and human kidney organoids. We confirmed that Notch signaling is needed for maturation of all nephron lineages, and thus mature lineage markers fail to detect a fate bias. By contrast, early markers identified a distal fate bias in cells lacking Notch2, and a concomitant increase in early proximal and podocyte fates in cells expressing hyperactive Notch1 was observed. Orthogonal support for a conserved role for Notch signaling in the distal/proximal axis segmentation is provided by the demonstration that Nicastrin-deficient hiPSCs-derived organoids differentiate into TFA2B+ distal tubule and CDH1 connecting segment progenitors, but not into HNF4A+ or LTL+ proximal progenitors.

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PFNF54-Pfs16-GFP-LUC gametocyte time course from commitment to maturity

Project description:Plasmodium falciparum gametocytes undergo 14 days of gametocytogenesis to generate mature, transmissible gametocytes. This timecourse delineates the transcriptional profiles of gametocytes from commitment to maturity.

2018-04-30 | GSE104889 | GEO

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