New England Journal of Medicine, Год журнала: 2024, Номер 391(12), С. 1162 - 1163
Опубликована: Сен. 25, 2024
Язык: Английский
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Июнь 1, 2024
Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary and causes significant morbidity, ultimately leading to end-stage disease. PKD pathogenesis characterized by complex dynamic alterations in multiple cell types during progression, hampering a deeper understanding of mechanism development therapeutic approaches. Here, we generate single nucleus multimodal atlas an orthologous mouse model at early, mid late timepoints, consisting 125,434 single-nucleus transcriptomic epigenetic multiomes. We catalogue differentially expressed genes activated regions each type characterizing cell-type-specific responses Pkd1 deletion. describe heterogeneous, atypical collecting duct cells as well proximal tubular that constitute cyst epithelia PKD. The transcriptional regulation lining marker GPRC5A conserved between human cystic epithelia, suggesting shared gene regulatory pathways. Our multiomic analysis provides foundation understand earliest changes molecular deregulation single-cell resolution.
Язык: Английский
Процитировано
2
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Июль 2, 2024
The kidney maintains body fluid homeostasis by reabsorbing essential compounds and excreting waste. Proximal tubule cells, crucial for renal reabsorption of a range sugars, ions, amino acids, are highly susceptible to damage, leading pathologies necessitating dialysis transplants. While human pluripotent stem cell-derived organoids used modeling development, disease, injury, the formation proximal nephron cells in these 3D structures is incomplete. Here, we describe how drive development precursors following blueprint
Язык: Английский
Процитировано
2
Nephrology Dialysis Transplantation, Год журнала: 2024, Номер unknown
Опубликована: Июль 25, 2024
The proximal tubule (PT) is known as the workhorse of kidney, both for range and magnitude functions that it performs. It not only responsible reabsorbing most solutes proteins filtered by glomeruli, but also secreting non-filtered substances including drugs uremic toxins. PT therefore plays a pivotal role in kidney physiology body homeostasis. Moreover, major site damage acute injury nephrotoxicity. In this review, we will provide an introduction to cell biology explore how adapted execution myriad different these can differ between males females. We then discuss regulates phosphate, glucose acid-base balance, consequences alterations function bone cardiovascular health. Finally, why vulnerable ischemic toxic insults, lead maladaptive repair, chronic damage, fibrosis. summary, demonstrate knowledge basic critical understanding disease phenotypes their associated systemic complications, developing new therapeutic strategies prevent these.
Язык: Английский
Процитировано
2
American Journal Of Pathology, Год журнала: 2024, Номер 195(1), С. 7 - 22
Опубликована: Сен. 26, 2024
Язык: Английский
Процитировано
2
New England Journal of Medicine, Год журнала: 2024, Номер 391(12), С. 1162 - 1163
Опубликована: Сен. 25, 2024
Язык: Английский
Процитировано
2