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An integrated organoid omics map extends modeling potential of kidney disease

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An integrated organoid omics map extends modeling potential of kidney disease. / Lassé, Moritz; El Saghir, Jamal; Berthier, Celine C; Eddy, Sean; Fischer, Matthew; Laufer, Sandra D; Kylies, Dominik; Hutzfeldt, Arvid; Bonin, Léna Lydie; Dumoulin, Bernhard; Menon, Rajasree; Vega-Warner, Virginia; Eichinger, Felix; Alakwaa, Fadhl; Fermin, Damian; Billing, Anja M; Minakawa, Akihiro; McCown, Phillip J; Rose, Michael P; Godfrey, Bradley; Meister, Elisabeth; Wiech, Thorsten; Noriega, Mercedes; Chrysopoulou, Maria; Brandts, Paul; Ju, Wenjun; Reinhard, Linda; Hoxha, Elion; Grahammer, Florian; Lindenmeyer, Maja T; Huber, Tobias B; Schlüter, Hartmut; Thiel, Steffen; Mariani, Laura H; Puelles, Victor G; Braun, Fabian; Kretzler, Matthias; Demir, Fatih; Harder, Jennifer L; Rinschen, Markus M.

in: NAT COMMUN, Jahrgang 14, Nr. 1, 4903, 14.08.2023.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Lassé, M, El Saghir, J, Berthier, CC, Eddy, S, Fischer, M, Laufer, SD, Kylies, D, Hutzfeldt, A, Bonin, LL, Dumoulin, B, Menon, R, Vega-Warner, V, Eichinger, F, Alakwaa, F, Fermin, D, Billing, AM, Minakawa, A, McCown, PJ, Rose, MP, Godfrey, B, Meister, E, Wiech, T, Noriega, M, Chrysopoulou, M, Brandts, P, Ju, W, Reinhard, L, Hoxha, E, Grahammer, F, Lindenmeyer, MT, Huber, TB, Schlüter, H, Thiel, S, Mariani, LH, Puelles, VG, Braun, F, Kretzler, M, Demir, F, Harder, JL & Rinschen, MM 2023, 'An integrated organoid omics map extends modeling potential of kidney disease', NAT COMMUN, Jg. 14, Nr. 1, 4903. https://doi.org/10.1038/s41467-023-39740-7

APA

Lassé, M., El Saghir, J., Berthier, C. C., Eddy, S., Fischer, M., Laufer, S. D., Kylies, D., Hutzfeldt, A., Bonin, L. L., Dumoulin, B., Menon, R., Vega-Warner, V., Eichinger, F., Alakwaa, F., Fermin, D., Billing, A. M., Minakawa, A., McCown, P. J., Rose, M. P., ... Rinschen, M. M. (2023). An integrated organoid omics map extends modeling potential of kidney disease. NAT COMMUN, 14(1), [4903]. https://doi.org/10.1038/s41467-023-39740-7

Vancouver

Lassé M, El Saghir J, Berthier CC, Eddy S, Fischer M, Laufer SD et al. An integrated organoid omics map extends modeling potential of kidney disease. NAT COMMUN. 2023 Aug 14;14(1). 4903. https://doi.org/10.1038/s41467-023-39740-7

Bibtex

@article{8ef13228aaca4aca84d782a24c7f4e75,
title = "An integrated organoid omics map extends modeling potential of kidney disease",
abstract = "Kidney 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.",
keywords = "Humans, Tumor Necrosis Factor-alpha/metabolism, Proteome/metabolism, Kidney, Kidney Diseases/genetics, Organoids/metabolism",
author = "Moritz Lass{\'e} and {El Saghir}, Jamal and Berthier, {Celine C} and Sean Eddy and Matthew Fischer and Laufer, {Sandra D} and Dominik Kylies and Arvid Hutzfeldt and Bonin, {L{\'e}na Lydie} and Bernhard Dumoulin and Rajasree Menon and Virginia Vega-Warner and Felix Eichinger and Fadhl Alakwaa and Damian Fermin and Billing, {Anja M} and Akihiro Minakawa and McCown, {Phillip J} and Rose, {Michael P} and Bradley Godfrey and Elisabeth Meister and Thorsten Wiech and Mercedes Noriega and Maria Chrysopoulou and Paul Brandts and Wenjun Ju and Linda Reinhard and Elion Hoxha and Florian Grahammer and Lindenmeyer, {Maja T} and Huber, {Tobias B} and Hartmut Schl{\"u}ter and Steffen Thiel and Mariani, {Laura H} and Puelles, {Victor G} and Fabian Braun and Matthias Kretzler and Fatih Demir and Harder, {Jennifer L} and Rinschen, {Markus M}",
note = "{\textcopyright} 2023. Springer Nature Limited.",
year = "2023",
month = aug,
day = "14",
doi = "10.1038/s41467-023-39740-7",
language = "English",
volume = "14",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - An integrated organoid omics map extends modeling potential of kidney disease

AU - Lassé, Moritz

AU - El Saghir, Jamal

AU - Berthier, Celine C

AU - Eddy, Sean

AU - Fischer, Matthew

AU - Laufer, Sandra D

AU - Kylies, Dominik

AU - Hutzfeldt, Arvid

AU - Bonin, Léna Lydie

AU - Dumoulin, Bernhard

AU - Menon, Rajasree

AU - Vega-Warner, Virginia

AU - Eichinger, Felix

AU - Alakwaa, Fadhl

AU - Fermin, Damian

AU - Billing, Anja M

AU - Minakawa, Akihiro

AU - McCown, Phillip J

AU - Rose, Michael P

AU - Godfrey, Bradley

AU - Meister, Elisabeth

AU - Wiech, Thorsten

AU - Noriega, Mercedes

AU - Chrysopoulou, Maria

AU - Brandts, Paul

AU - Ju, Wenjun

AU - Reinhard, Linda

AU - Hoxha, Elion

AU - Grahammer, Florian

AU - Lindenmeyer, Maja T

AU - Huber, Tobias B

AU - Schlüter, Hartmut

AU - Thiel, Steffen

AU - Mariani, Laura H

AU - Puelles, Victor G

AU - Braun, Fabian

AU - Kretzler, Matthias

AU - Demir, Fatih

AU - Harder, Jennifer L

AU - Rinschen, Markus M

N1 - © 2023. Springer Nature Limited.

PY - 2023/8/14

Y1 - 2023/8/14

N2 - Kidney 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.

AB - Kidney 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.

KW - Humans

KW - Tumor Necrosis Factor-alpha/metabolism

KW - Proteome/metabolism

KW - Kidney

KW - Kidney Diseases/genetics

KW - Organoids/metabolism

U2 - 10.1038/s41467-023-39740-7

DO - 10.1038/s41467-023-39740-7

M3 - SCORING: Journal article

C2 - 37580326

VL - 14

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

M1 - 4903

ER -