03086nas a2200685   4500000000100000000000100001008004100002260001500043653003900058653002900097653002000126653002200146653001500168100001800183700002000201700002300221700001400244700002000258700002100278700001900299700002000318700002200338700002200360700001900382700002500401700002000426700001800446700001800464700002000482700002100502700002200523700002000545700002000565700002200585700001900607700002100626700002300647700001700670700001400687700001900701700001600720700002200736700002400758700002000782700002200802700001800824700002100842700002200863700001700885700002200902700001600924700002300940700002300963245008200986856005501068300000901123490000701132520124701139022001402386       2023                            d  c2023-08-1410aFocal segmental glomerulosclerosis10aGene expression analysis10aKidney diseases10aMass spectrometry10aProteomics1 aMoritz Lassé1 aJamal El Saghir1 aCeline C. Berthier1 aSean Eddy1 aMatthew Fischer1 aSandra D. Laufer1 aDominik Kylies1 aArvid Hutzfeldt1 aLéna Lydie Bonin1 aBernhard Dumoulin1 aRajasree Menon1 aVirginia Vega-Warner1 aFelix Eichinger1 aFadhl Alakwaa1 aDamian Fermin1 aAnja M. Billing1 aAkihiro Minakawa1 aPhillip J. McCown1 aMichael P. Rose1 aBradley Godfrey1 aElisabeth Meister1 aThorsten Wiech1 aMercedes Noriega1 aMaria Chrysopoulou1 aPaul Brandts1 aWenjun Ju1 aLinda Reinhard1 aElion Hoxha1 aFlorian Grahammer1 aMaja T. Lindenmeyer1 aTobias B. Huber1 aHartmut Schlüter1 aSteffen Thiel1 aLaura H. Mariani1 aVictor G. Puelles1 aFabian Braun1 aMatthias Kretzler1 aFatih Demir1 aJennifer L. Harder1 aMarkus M. Rinschen00aAn integrated organoid omics map extends modeling potential of kidney disease  uhttps://www.nature.com/articles/s41467-023-39740-7  a49030 v143 aKidney organoids are a promising model to study kidney disease, but their use is constrained by limited knowledge of their functional protein expression profile. Here, we define the organoid proteome and transcriptome trajectories over culture duration and upon exposure to TNFα, a cytokine stressor. Older organoids increase deposition of extracellular matrix but decrease expression of glomerular proteins. Single cell transcriptome integration reveals that most proteome changes localize to podocytes, tubular and stromal cells. TNFα treatment of organoids results in 322 differentially expressed proteins, including cytokines and complement components. Transcript expression of these 322 proteins is significantly higher in individuals with poorer clinical outcomes in proteinuric kidney disease. Key TNFα-associated protein (C3 and VCAM1) expression is increased in both human tubular and organoid kidney cell populations, highlighting the potential for organoids to advance biomarker development. By integrating kidney organoid omic layers, incorporating a disease-relevant cytokine stressor and comparing with human data, we provide crucial evidence for the functional relevance of the kidney organoid model to human kidney disease.  a2041-1723