High tonicity drives mammalian kidney maturation, allowing human collecting duct organoids to acquire vasopressin responsiveness and model congenital nephrogenic diabetes insipidus.
Urinary biomarkers of tubular stress and congestion (L-FABP, NGAL, tAM) do not significantly correlate with diuretic response in patients hospitalized for acute heart failure.
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tonicity.This maturation process was mainly dependent on NFAT5.In scRNA-seq analysis, mouse CD organoids cultured at high tonicity in the presence of vasopressin and aldosterone overlapped with postnatal day 7 medullary CDs with high expression levels of marker genes such as Aqp2 and Slc14a2.Additionally, we have established a maturation protocol for human CD organoids.These organoids also underwent morphological and transcriptional maturation and acquired vasopressin responsiveness at high tonicity.scRNA-seq analysis revealed that the mature CD organoids exhibited comparable expression levels of maturation markers to those of adult CDs.Finally, the mature CD organoids induced from iPSCs harboring a causative AVPR2 mutation of congenital NDI lost vasopressin responsiveness.In contrast, the healthy organoids responded to vasopressin with clear AQP2 expression in the apical membrane.Conclusion: High tonicity is a driving force not only for urine concentration, but also for mammalian kidney maturation.Our mature CD organoids reached a postnatal stage, and potentially an adult stage.Our study uncovers a novel principle of kidney maturation triggered by environmental cues and offers a promising approach to maximize the potential of kidney organoids for future therapies.I have no potential conflict of interest to disclose.I did not use generative AI and AI-assisted technologies in the writing process.
Hirai et al. (Wed,) reported a other. High tonicity drives mammalian kidney maturation, allowing human collecting duct organoids to acquire vasopressin responsiveness and model congenital nephrogenic diabetes insipidus.