IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32972-z.html
   My bibliography  Save this article

Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression

Author

Listed:
  • Parker C. Wilson

    (Washington University in St. Louis)

  • Yoshiharu Muto

    (Washington University in St. Louis)

  • Haojia Wu

    (Washington University in St. Louis)

  • Anil Karihaloo

    (Novo Nordisk Research Center Seattle Inc)

  • Sushrut S. Waikar

    (Boston University School of Medicine, Boston Medical Center)

  • Benjamin D. Humphreys

    (Washington University in St. Louis
    Washington University in St. Louis)

Abstract

The proximal tubule is a key regulator of kidney function and glucose metabolism. Diabetic kidney disease leads to proximal tubule injury and changes in chromatin accessibility that modify the activity of transcription factors involved in glucose metabolism and inflammation. Here we use single nucleus RNA and ATAC sequencing to show that diabetic kidney disease leads to reduced accessibility of glucocorticoid receptor binding sites and an injury-associated expression signature in the proximal tubule. We hypothesize that chromatin accessibility is regulated by genetic background and closely-intertwined with metabolic memory, which pre-programs the proximal tubule to respond differently to external stimuli. Glucocorticoid excess has long been known to increase risk for type 2 diabetes, which raises the possibility that glucocorticoid receptor inhibition may mitigate the adverse metabolic effects of diabetic kidney disease.

Suggested Citation

  • Parker C. Wilson & Yoshiharu Muto & Haojia Wu & Anil Karihaloo & Sushrut S. Waikar & Benjamin D. Humphreys, 2022. "Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32972-z
    DOI: 10.1038/s41467-022-32972-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32972-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32972-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Olivier Delaneau & Jean-François Zagury & Matthew R. Robinson & Jonathan L. Marchini & Emmanouil T. Dermitzakis, 2019. "Accurate, scalable and integrative haplotype estimation," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    2. Jill E. Moore & Michael J. Purcaro & Henry E. Pratt & Charles B. Epstein & Noam Shoresh & Jessika Adrian & Trupti Kawli & Carrie A. Davis & Alexander Dobin & Rajinder Kaul & Jessica Halow & Eric L. No, 2020. "Expanded encyclopaedias of DNA elements in the human and mouse genomes," Nature, Nature, vol. 583(7818), pages 699-710, July.
    3. Robin Andersson & Claudia Gebhard & Irene Miguel-Escalada & Ilka Hoof & Jette Bornholdt & Mette Boyd & Yun Chen & Xiaobei Zhao & Christian Schmidl & Takahiro Suzuki & Evgenia Ntini & Erik Arner & Eivi, 2014. "An atlas of active enhancers across human cell types and tissues," Nature, Nature, vol. 507(7493), pages 455-461, March.
    4. Alexander Teumer & Yong Li & Sahar Ghasemi & Bram P. Prins & Matthias Wuttke & Tobias Hermle & Ayush Giri & Karsten B. Sieber & Chengxiang Qiu & Holger Kirsten & Adrienne Tin & Audrey Y. Chu & Nisha B, 2019. "Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria," Nature Communications, Nature, vol. 10(1), pages 1-19, December.
    5. Kip D. Zimmerman & Mark A. Espeland & Carl D. Langefeld, 2021. "A practical solution to pseudoreplication bias in single-cell studies," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    6. Angli Xue & Yang Wu & Zhihong Zhu & Futao Zhang & Kathryn E. Kemper & Zhili Zheng & Loic Yengo & Luke R. Lloyd-Jones & Julia Sidorenko & Yeda Wu & Allan F. McRae & Peter M. Visscher & Jian Zeng & Jian, 2018. "Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    7. Bates, Douglas & Mächler, Martin & Bolker, Ben & Walker, Steve, 2015. "Fitting Linear Mixed-Effects Models Using lme4," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 67(i01).
    8. Rongxin Fang & Sebastian Preissl & Yang Li & Xiaomeng Hou & Jacinta Lucero & Xinxin Wang & Amir Motamedi & Andrew K. Shiau & Xinzhu Zhou & Fangming Xie & Eran A. Mukamel & Kai Zhang & Yanxiao Zhang & , 2021. "Comprehensive analysis of single cell ATAC-seq data with SnapATAC," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    9. Raha Pazoki & Evangelos Evangelou & David Mosen-Ansorena & Rui Climaco Pinto & Ibrahim Karaman & Paul Blakeley & Dipender Gill & Verena Zuber & Paul Elliott & Ioanna Tzoulaki & Abbas Dehghan, 2019. "GWAS for urinary sodium and potassium excretion highlights pathways shared with cardiovascular traits," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    10. Joshua Chiou & Ryan J. Geusz & Mei-Lin Okino & Jee Yun Han & Michael Miller & Rebecca Melton & Elisha Beebe & Paola Benaglio & Serina Huang & Katha Korgaonkar & Sandra Heller & Alexander Kleger & Seba, 2021. "Interpreting type 1 diabetes risk with genetics and single-cell epigenomics," Nature, Nature, vol. 594(7863), pages 398-402, June.
    11. Tsukasa Kouno & Jonathan Moody & Andrew Tae-Jun Kwon & Youtaro Shibayama & Sachi Kato & Yi Huang & Michael Böttcher & Efthymios Motakis & Mickaël Mendez & Jessica Severin & Joachim Luginbühl & Imad Ab, 2019. "C1 CAGE detects transcription start sites and enhancer activity at single-cell resolution," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    12. Xinsheng Nan & Huck-Hui Ng & Colin A. Johnson & Carol D. Laherty & Bryan M. Turner & Robert N. Eisenman & Adrian Bird, 1998. "Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex," Nature, Nature, vol. 393(6683), pages 386-389, May.
    13. Jacklyn N. Hellwege & Digna R. Velez Edwards & Ayush Giri & Chengxiang Qiu & Jihwan Park & Eric S. Torstenson & Jacob M. Keaton & O. D. Wilson & Cassianne Robinson-Cohen & Cecilia P. Chung & Christian, 2019. "Mapping eGFR loci to the renal transcriptome and phenome in the VA Million Veteran Program," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Haojia Wu & Eryn E. Dixon & Qiao Xuanyuan & Juanru Guo & Yasuhiro Yoshimura & Chitnis Debashish & Anezka Niesnerova & Hao Xu & Morgane Rouault & Benjamin D. Humphreys, 2024. "High resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Wei E. Gordon & Seungbyn Baek & Hai P. Nguyen & Yien-Ming Kuo & Rachael Bradley & Sarah L. Fong & Nayeon Kim & Alex Galazyuk & Insuk Lee & Melissa R. Ingala & Nancy B. Simmons & Tony Schountz & Lisa N, 2024. "Integrative single-cell characterization of a frugivorous and an insectivorous bat kidney and pancreas," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    3. Nicolas Ledru & Parker C. Wilson & Yoshiharu Muto & Yasuhiro Yoshimura & Haojia Wu & Dian Li & Amish Asthana & Stefan G. Tullius & Sushrut S. Waikar & Giuseppe Orlando & Benjamin D. Humphreys, 2024. "Predicting proximal tubule failed repair drivers through regularized regression analysis of single cell multiomic sequencing," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Suhas V. Vasaikar & Adam K. Savage & Qiuyu Gong & Elliott Swanson & Aarthi Talla & Cara Lord & Alexander T. Heubeck & Julian Reading & Lucas T. Graybuck & Paul Meijer & Troy R. Torgerson & Peter J. Sk, 2023. "A comprehensive platform for analyzing longitudinal multi-omics data," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Sudha Sunil Rajderkar & Kitt Paraiso & Maria Luisa Amaral & Michael Kosicki & Laura E. Cook & Fabrice Darbellay & Cailyn H. Spurrell & Marco Osterwalder & Yiwen Zhu & Han Wu & Sarah Yasmeen Afzal & Ma, 2024. "Dynamic enhancer landscapes in human craniofacial development," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. JANSSENS, Jochen & DE CORTE, Annelies & SÖRENSEN, Kenneth, 2016. "Water distribution network design optimisation with respect to reliability," Working Papers 2016007, University of Antwerp, Faculty of Business and Economics.
    4. Raymond Hernandez & Elizabeth A. Pyatak & Cheryl L. P. Vigen & Haomiao Jin & Stefan Schneider & Donna Spruijt-Metz & Shawn C. Roll, 2021. "Understanding Worker Well-Being Relative to High-Workload and Recovery Activities across a Whole Day: Pilot Testing an Ecological Momentary Assessment Technique," IJERPH, MDPI, vol. 18(19), pages 1-17, October.
    5. Christopher Hassall & Michael Nisbet & Evan Norcliffe & He Wang, 2024. "The Potential Health Benefits of Urban Tree Planting Suggested through Immersive Environments," Land, MDPI, vol. 13(3), pages 1-12, February.
    6. Jie Zhao & Ji Chen & Damien Beillouin & Hans Lambers & Yadong Yang & Pete Smith & Zhaohai Zeng & Jørgen E. Olesen & Huadong Zang, 2022. "Global systematic review with meta-analysis reveals yield advantage of legume-based rotations and its drivers," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    7. Elisabeth Beckmann & Lukas Olbrich & Joseph Sakshaug, 2024. "Multivariate assessment of interviewer-related errors in a cross-national economic survey (Lukas Olbrich, Elisabeth Beckmann, Joseph W. Sakshaug)," Working Papers 253, Oesterreichische Nationalbank (Austrian Central Bank).
    8. F J Heather & D Z Childs & A M Darnaude & J L Blanchard, 2018. "Using an integral projection model to assess the effect of temperature on the growth of gilthead seabream Sparus aurata," PLOS ONE, Public Library of Science, vol. 13(5), pages 1-19, May.
    9. Kip D. Zimmerman & Ciaran Evans & Carl D. Langefeld, 2022. "Reply to: A balanced measure shows superior performance of pseudobulk methods in single-cell RNA-sequencing analysis," Nature Communications, Nature, vol. 13(1), pages 1-2, December.
    10. Valentina Krenz & Arjen Alink & Tobias Sommer & Benno Roozendaal & Lars Schwabe, 2023. "Time-dependent memory transformation in hippocampus and neocortex is semantic in nature," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Morán-Ordóñez, Alejandra & Ameztegui, Aitor & De Cáceres, Miquel & de-Miguel, Sergio & Lefèvre, François & Brotons, Lluís & Coll, Lluís, 2020. "Future trade-offs and synergies among ecosystem services in Mediterranean forests under global change scenarios," Ecosystem Services, Elsevier, vol. 45(C).
    12. Jack McDonnell & Thomas McKenna & Kathryn A. Yurkonis & Deirdre Hennessy & Rafael Andrade Moral & Caroline Brophy, 2023. "A Mixed Model for Assessing the Effect of Numerous Plant Species Interactions on Grassland Biodiversity and Ecosystem Function Relationships," Journal of Agricultural, Biological and Environmental Statistics, Springer;The International Biometric Society;American Statistical Association, vol. 28(1), pages 1-19, March.
    13. Ana Pinto & Tong Yin & Marion Reichenbach & Raghavendra Bhatta & Pradeep Kumar Malik & Eva Schlecht & Sven König, 2020. "Enteric Methane Emissions of Dairy Cattle Considering Breed Composition, Pasture Management, Housing Conditions and Feeding Characteristics along a Rural-Urban Gradient in a Rising Megacity," Agriculture, MDPI, vol. 10(12), pages 1-18, December.
    14. Damian M. Herz & Manuel Bange & Gabriel Gonzalez-Escamilla & Miriam Auer & Keyoumars Ashkan & Petra Fischer & Huiling Tan & Rafal Bogacz & Muthuraman Muthuraman & Sergiu Groppa & Peter Brown, 2022. "Dynamic control of decision and movement speed in the human basal ganglia," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    15. Kathrin Stenchly & Marc Victor Hansen & Katharina Stein & Andreas Buerkert & Wilhelm Loewenstein, 2018. "Income Vulnerability of West African Farming Households to Losses in Pollination Services: A Case Study from Ouagadougou, Burkina Faso," Sustainability, MDPI, vol. 10(11), pages 1-12, November.
    16. Dongyan Liu & Chongran Zhou & John K. Keesing & Oscar Serrano & Axel Werner & Yin Fang & Yingjun Chen & Pere Masque & Janine Kinloch & Aleksey Sadekov & Yan Du, 2022. "Wildfires enhance phytoplankton production in tropical oceans," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    17. Zhaogeng Yang & Yanhui Li & Peijin Hu & Jun Ma & Yi Song, 2020. "Prevalence of Anemia and its Associated Factors among Chinese 9-, 12-, and 14-Year-Old Children: Results from 2014 Chinese National Survey on Students Constitution and Health," IJERPH, MDPI, vol. 17(5), pages 1-10, February.
    18. Marco Lopez-Cruz & Fernando M. Aguate & Jacob D. Washburn & Natalia Leon & Shawn M. Kaeppler & Dayane Cristina Lima & Ruijuan Tan & Addie Thompson & Laurence Willard Bretonne & Gustavo los Campos, 2023. "Leveraging data from the Genomes-to-Fields Initiative to investigate genotype-by-environment interactions in maize in North America," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    19. Baumann, Elias & Kern, Jana & Lessmann, Stefan, 2019. "Usage Continuance in Software-as-a-Service," IRTG 1792 Discussion Papers 2019-005, Humboldt University of Berlin, International Research Training Group 1792 "High Dimensional Nonstationary Time Series".
    20. Alexandra M. Cheney & Stephanann M. Costello & Nicholas V. Pinkham & Annie Waldum & Susan C. Broadaway & Maria Cotrina-Vidal & Marc Mergy & Brian Tripet & Douglas J. Kominsky & Heather M. Grifka-Walk , 2023. "Gut microbiome dysbiosis drives metabolic dysfunction in Familial dysautonomia," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32972-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.